Modified nucleases

ABSTRACT

Provided herein are methods and compositions utilizing modified nucleases and/or other components, such as guide nucleic acids and donor templates, for use in a CRISPR system.

CROSS-REFERENCE

This application is a continuation of PCT/US2022/028208, filed May 6, 2022, which claims priority to U.S. Provisional Application No. 63/185,315, filed May 6, 2021, and to U.S. Provisional Application No. 63/315,483, filed Mar. 1, 2022, both of which are incorporated herein by reference.

SEQUENCE LISTING

The instant application contains a Sequence Listing which has been submitted electronically in XML file format and is hereby incorporated by reference in its entirety. Said XML copy, created on Jun. 16, 2023, is named ARTN-008_CON-T1_SL.xml and is 985,959 bytes in size.

BACKGROUND

Nucleic acid-guided nucleases have become important tools for research and genome engineering. The applicability of these tools can be limited by the sequence specificity requirements, expression, or delivery issues.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:

FIG. 1 shows a diagram of MAD7 comprising one or more nuclear localization signals (NLS). FIG. 1 discloses “His6” as SEQ ID NO: 423.

FIG. 2 shows editing frequency at the DNMT1 locus in and post-transfection cell viability of T-cell leukemic cells following treatment comprising one or more guide nucleic acids complexed with MAD7 comprising one or more NLS.

FIG. 3 shows editing frequency at the DNMT1 locus in T-cell leukemic cells using multiple electroporation programs in combination with the SE electroporation buffer.

FIG. 4 shows editing frequency at the DNMT1 locus in T-cell leukemic cells using multiple electroporation programs in combination with the SF electroporation buffer.

FIG. 5 shows editing frequency at the DNMT1 locus in T-cell leukemic cells using multiple electroporation programs in combination with the SG electroporation buffer.

FIG. 6 shows editing frequency at the DNMT1 locus in T-cell leukemic cells using multiple electroporation programs.

FIG. 7 shows editing frequency by type at eight loci in T-cell leukemic cells using multiple guide nucleic acids complexed with MAD7 comprising one or more NLS.

FIG. 8 shows a comparison of editing efficiency between T-cell leukemic cells treated with MAD7 comprising one or more guide nucleic acids targeting the DNMT1 locus as compared to a control guide nucleic acid binned by editing frequency.

FIG. 9 shows editing frequency by PAM motif in T-cell leukemic cells using multiple guide nucleic acids complexed with MAD7 comprising one or more NLS.

FIG. 10A shows sequence logo plots for multiple guide nucleic acids binned by editing frequency in T-cell leukemic cells using when complexed with MAD7 comprising one or more NLS.

FIG. 10B shows nucleotide and dinucleotide frequency for multiple guide nucleic acids binned by editing frequency in T-cell leukemic cells using when complexed with MAD7 comprising one or more NLS.

FIG. 11 shows trinucleotide AAA or UUU frequency binned by editing frequency in T-cell leukemic cells following treatment with multiple guide nucleic acids complexed with MAD7 comprising one or more NLS.

FIG. 12 shows editing frequency for both INDELs and frameshift mutations at eight loci in T-cell leukemic cells following treatment with multiple guide nucleic acids complexed with MAD7 comprising one or more NLS.

FIG. 13 shows the correlation between INDEL frequency in the gNA validation experiment versus INDEL formation in the gNA screen experiment.

FIG. 14 shows the proportion of frameshift to INDELs at eight loci in T-cell leukemic cells following treatment with multiple guide nucleic acids complexed with MAD7 comprising one or more NLS.

FIG. 15 shows INDEL frequency for gNAs comprising representative spacer sequences complexed with MAD7 comprising one or more NLS in T-cell leukemic cells at predicted off-target sites. FIG. 15 discloses SEQ ID NOS 424-427, 427-429 and 429-454, respectively, in order of appearance.

FIG. 16 shows INDEL frequency for gNAs comprising representative spacer sequences complexed with MAD7 comprising one or more NLS in T-cell leukemic cells at predicted off-target sites. FIG. 16 discloses SEQ ID NOS 455-484, 453-454 and 485-487, respectively, in order of appearance.

FIG. 17 shows INDEL frequency at the AAVS1 locus in T-cell leukemic cells following treatment with a gNA:MAD7 complex.

FIG. 18 shows GFP insertion efficiency at the AAVS1 locus and cell viability following treatment for multiple primer constructs.

FIG. 19 shows GFP insertion efficiency at the AAVS1 locus with increasing concentrations of donor template (e.g., HDRT) and variable homology arm length.

FIG. 20 shows CAR insertion efficiency at the AAVS1 locus and cell viability with increasing concentrations of donor template and variable homology arm length.

FIG. 21 shows CAR insertion efficiency (A) at the AAVS1 locus and cell viability (B) in primary T-cells.

DETAILED DESCRIPTION

CRISPR is an abbreviation of Clustered Regularly Interspaced Short Palindromic Repeats. In a palindromic repeat, the sequence of nucleotides is the same in both directions. Each of these palindromic repetitions is followed by short segments of spacer DNA. Small clusters of Cas (CRISPR-associated system) genes are located next to CRISPR sequences. The CRISPR/Cas system is a prokaryotic immune system that can confer resistance to foreign genetic elements such as those present within plasmids and phages providing the prokaryote a form of acquired immunity. RNA harboring a spacer sequence assists Cas (CRISPR-associated) proteins to recognize and cut exogenous DNA. CRISPR sequences are found in approximately 50% of bacterial genomes and nearly 90% of sequenced archaea has selected for efficient and robust metabolic and regulatory networks that prevent unnecessary metabolite biosynthesis and optimally distribute resources to maximize overall cellular fitness. The complexity of these networks with limited approaches to understand their structure and function and the ability to re-program cellular networks to modify these systems for a diverse range of applications has complicated advances in this space. Certain approaches to re-program cellular networks are directed to modifying single genes of complex pathways but as a consequence of modifying single genes, unwanted modifications to the genes or other genes can result, getting in the way of identifying changes necessary to achieve a sought-after endpoint as well as complicating the endpoint sought by the modification.

CRISPR-Cas driven genome editing and engineering has dramatically impacted biology and biotechnology in general. CRISPR-Cas editing systems require a polynucleotide guided nuclease, a guide nucleic acid (gNA) e.g. a guide RNA (gRNA)) that directs the nuclease to cut a specific region of the genome, and, optionally, a donor DNA cassette (also referred to herein as a donor template or editing sequence) that can be used to repair the cut dsDNA and thereby incorporate programmable edits at the site of interest. The earliest demonstrations and applications of CRISPR-Cas editing used Cas9 nucleases and associated gRNA. These systems have been used for gene editing in a broad range of species encompassing bacteria to higher order mammalian systems such as animals and in certain cases, humans. It is well established, however, that important editing parameters such as protospacer adjacent motif (PAM) specificity, editing efficiency, and off-target rates, among others, are species, loci, and nuclease dependent. There is increasing interest in identifying and rapidly characterizing novel nuclease systems that can be exploited to broaden and improve overall editing capabilities.

One version of the CRISPR/Cas system, CRISPR/Cas9, has been modified to provide useful tools for editing targeted genomes. By delivering the Cas9 nuclease complexed with a synthetic guide RNA (gRNA) into a cell, the cell's genome can be cut/edited at a predetermined location, allowing existing genes to be removed and/or new ones added. These systems are useful but have some important limitations regarding efficiency and accuracy of targeted editing, imprecise editing complications, as well as impediments when used for commercially relevant situations such as gene replacement. Therefore, a need exists for improved nucleic acid guided nuclease systems for directed and accurate editing with improved efficiency.

As used herein, the term “modulating” and “manipulating” of genome editing can mean an increase, a decrease, upregulation, downregulation, induction, a change in editing activity, a change in binding, a change cleavage or the like, of one or more of targeted genes or gene clusters of certain embodiments disclosed herein.

In certain embodiments of the present disclosure, there can be employed conventional molecular biology, microbiology, and recombinant DNA techniques within the skill of the art. Such techniques are explained fully in the literature and understood by those of skill in the art.

In other embodiments, primers used herein for preparation per conventional techniques can include sequencing primers and amplification primers. In some embodiments, plasmids and oligomers used in conventional techniques can include synthesized oligomers and oligomer cassettes.

In some embodiments disclosed herein, nucleic acid-guided nuclease systems and methods of use are provided. A nuclease system can include transcripts and other elements involved in the expression of an engineered nuclease disclosed herein, which can include sequences encoding a novel engineered nucleic acid-guided nuclease protein and a guide sequence (gRNA) or a novel gRNA as disclosed herein. In some embodiments, nucleic acid-guided nuclease systems can include at least one CRISPR-associated nucleic acid guided nuclease construct, the disclosure of which are provided herein. In other embodiments, nucleic acid-guided nuclease systems can include at least one known guide sequence (gRNA) or at least one novel gRNA, such as a single gRNA or a dual gRNA. In some embodiments, an engineered nucleic acid-guided nuclease of the instant invention can be used in systems for editing a gene of interest in humans or other species.

Bacterial and archaeal targetable nuclease systems have emerged as powerful tools for precision genome editing. However, naturally occurring nucleases have some limitations including expression and delivery challenges due to the nucleic acid sequence and protein size. In certain embodiments, novel engineered nucleic acid-guided nuclease constructs disclosed herein can be created for targeting of a targeted gene and/or increased efficiency and/or accuracy of targeted gene editing in a subject.

In accordance with these embodiments, it is known that Cas12a is a single RNA-guided CRISPR/Cas endonuclease capable of genome editing having differing features when compared to Cas9. In certain embodiments, a Cas12a-based system allow fast and reliable introduction of donor DNA into a genome. In addition, Cas12a broadens genome editing. CRISPR/Cas12a genome editing has been evaluated in human cells as well as other organisms including plants. Several features of the CRISPR/Cas12a system are different when compared to CRISPR/Cas9.

It is known that Cas12a nuclease recognizes T-rich protospacer adjacent motif (PAM) sequences (e.g. 5′-TTTN-3′ (AsCas12a, LbCas12a) and 5′-TTN-3′ (FnCas12a); whereas, the comparable sequence for SpCas9 is NGG. The PAM sequence of Cas12a is located at the 5′ end of the target DNA sequence, where it is at the 3′ end for Cas9. In addition, Cas12a is capable of cleaving DNA distal to its PAM around the +18/+23 position of the protospacer. This cleavage creates a staggered DNA overhang (e.g. sticky ends), whereas Cas9 cleaves close to its PAM after the 3′ position of the protospacer at both strands and creates blunt ends. In certain methods, creating altered recognition of nucleases can provide an improvement over Cas9 or Cas12a to improve accuracy. Further, Cas12a is guided by a single crRNA and does not require a tracrRNA, resulting in a shorter gRNA sequence than the sgRNA used by Cas9. Surprisingly, it has been found that the modified Cas12a nucleases provided herein can also function with a dual gRNA.

It is also known that Cas12a displays additional ribonuclease activity that functions in crRNA processing. Cas12a is used as an editing tool for different species (e.g. S. cerevisiae), allowing the use of an alternative PAM sequence compared with the one recognized by CRISPR/Cas9. Novel nucleases disclosed herein can further recognize the same or alternative PAM sequences. These novel nucleases can provide an alternative system for multiplex genome editing as compared with known multiplex approaches and can be used as an improved system in mammalian gene editing.

Well-known Cas12a protein-RNA complexes recognize a T-rich PAM and cleavage leads to a staggered DNA double-stranded break. Cas12a-type nuclease interacts with the pseudoknot structure formed by the 5′-handle of crRNA. A guide RNA segment, composed of a seed region and the 3′ terminus, possesses complementary binding sequences with the target DNA sequences. Cas12a type nucleases characterized to date have been demonstrated to work with a single gRNA and to process gRNA arrays. While Cas12a-type and Cas9 nuclease systems have proven highly impactful, neither system has been demonstrated to function as predictably as is desired to enable the full range of applications envisioned for gene-editing technologies.

In the current state, a range of efforts have attempted to engineer improved CRISPR editing systems having increased efficiency and accuracy, which have included engineering of the PAM specificity, stability, and sequence of the gRNA and-or the nuclease. For example, chemical modifications of CRISPR/Cas9 gRNA expected to increase gRNA stability was found to lead to a 3.8-fold higher indel frequencies in human cells. In addition, other studies included structure-guided mutagenesis of Cas12a and screened to identify variants with an increased range of recognized PAM sequences. These engineered AsCas12a recognized TYCV and TATV PAMs in addition to the established TTTV sequence, with enhanced activities in vitro and in tested human cells.

In certain embodiments, Cas12a-like nucleases and engineered gRNAs disclosed herein are contemplated for use in bacteria, and other prokaryotes. In certain embodiments, engineered designer nucleases are contemplated for use in eukaryotes such as yeast, mammals, e.g., human as well as of use in birds and fish, or cells derived from same.

In some embodiments, off-targeting rates for nuclease constructs disclosed herein can be reduced compared to a control, e.g., a native sequence, for improved editing. Off-targeting rates can be readily tested.

In some embodiments, nuclease constructs disclosed herein can share conserved encoded motifs of known nucleases. In other embodiments, nuclease constructs disclosed herein do not share conserved encoded peptide motifs with known nucleases. In preferred embodiments, provided herein are compositions, methods, and/or kits wherein the CRISPR nuclease comprises a Type V nuclease. In certain embodiments, provided herein are compositions, methods, and/or kits wherein the CRISPR nuclease comprises a Type V-A, V-B, V-C, V-D, or V-E CRISPR nuclease. In certain embodiments, provided herein are compositions, methods, and/or kits wherein the CRISPR nuclease comprises a Type V-A nuclease. Naturally occurring type V-A CRISPR nucleases comprise a RuvC-like nuclease domain but lack an HNH endonuclease domain, and recognize a 5′ T-rich PAM located immediately upstream from the target nucleotide sequence, the orientation determined using the non-target strand (i.e., the strand not hybridized with the spacer sequence) as the coordinate. These CRISPR nucleases cleave a double-stranded DNA to generate a staggered double-stranded break rather than a blunt end. The cleavage site is distant from the PAM site (e.g., separated by at least 10, 11, 12, 13, 14, or 15 nucleotides downstream from the PAM on the non-target strand and/or separated by at least 15, 16, 17, 18, or 19 nucleotides upstream from the sequence complementary to PAM on the target strand).

In certain embodiments, a type V-A CRISPR nuclease comprises Cpf1. Cpf1 proteins are known in the art and are described, e.g., in U.S. Pat. Nos. 9,790,490 and 10,113,179. Cpf1 orthologs can be found in various bacterial and archaeal genomes. For example, in certain embodiments, the Cpf1 protein is derived from Francisella novicida U112 (Fn), Acidaminococcus sp. BV3L6 (As), Lachnospiraceae bacterium ND2006 (Lb), Lachnospiraceae bacterium MA2020 (Lb2), Candidatus Methanoplasma termitum (CMt), Moraxella bovoculi 237 (Mb), Porphyromonas crevioricanis (Pc), Prevotella disiens (Pd), Francisella tularensis 1, Francisella tularensis subsp. novicida, Prevotella albensis, Lachnospiraceae bacterium MC2017 1, Butyrivibrio proteoclasticus, Peregrinibacteria bacterium GW2011_GWA2_33_10, Parcubacteria bacterium GW2011_GWC2_44_17, Smithella sp. SCADC, Eubacterium eligens, Leptospira inadai, Porphyromonas macacae, Prevotella bryantii, Proteocatella sphenisci, Anaerovibrio sp. RM50, Moraxella caprae, Lachnospiraceae bacterium COE1, or Eubacterium coprostanoligenes.

In certain embodiments, a type V-A CRISPR nuclease comprises AsCpf1 or a variant thereof. In certain embodiments, a type V-A CRISPR nucleases comprises an amino acid sequence at least 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 3 of International (PCT) Application Publication No. WO 2021/158918. In certain embodiments, a type V-A CRISPR nucleases comprises the amino acid sequence set forth in SEQ ID NO: 3 of International (PCT) Application Publication No. WO 2021/158918.

In certain embodiments, a type V-A CRISPR nuclease comprises LbCpf1 or a variant thereof. In certain embodiments, a type V-A CRISPR nucleases comprises an amino acid sequence at least 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 4 of International (PCT) Application Publication No. WO 2021158918. In certain embodiments, a type V-A Cas protein comprises the amino acid sequence set forth in SEQ ID NO: 4 of International (PCT) Application Publication No. WO 2021/158918.

In certain embodiments, a type V-A CRISPR nuclease comprises FnCpf1 or a variant thereof. In certain embodiments, a type V-A Cas protein comprises an amino acid sequence at least 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 5 of International (PCT) Application Publication No. WO 2021158918. In certain embodiments, a type V-A Cas protein comprises the amino acid sequence set forth in SEQ ID NO: 5 of International (PCT) Application Publication No. WO 2021/158918.

In certain embodiments, a type V-A CRISPR nuclease comprises Prevotella bryantii Cpf1 (PbCpf1) or a variant thereof. In certain embodiments, a type V-A Cas protein comprises an amino acid sequence at least 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 6 of International (PCT) Application Publication No. WO 2021/158918. In certain embodiments, a type V-A Cas protein comprises the amino acid sequence set forth in SEQ ID NO: 6 of International (PCT) Application Publication No. WO 2021/158918.

In certain embodiments, a type V-A CRISPR nuclease comprises Proteocatella sphenisci Cpf1 (PsCpf1) or a variant thereof. In certain embodiments, a type V-A Cas protein comprises an amino acid sequence at least 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 7 of International (PCT) Application Publication No. WO 2021158918. In certain embodiments, a type V-A Cas protein comprises the amino acid sequence set forth in SEQ ID NO: 7 of International (PCT) Application Publication No. WO 2021/158918.

In certain embodiments, a type V-A CRISPR nuclease comprises Anaerovibrio sp. RM50 Cpf1 (As2Cpf1) or a variant thereof. In certain embodiments, a type V-A Cas protein comprises an amino acid sequence at least 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 8 of International (PCT) Application Publication No. WO 2021158918. In certain embodiments, a type V-A Cas protein comprises the amino acid sequence set forth in SEQ ID NO: 8 of International (PCT) Application Publication No. WO 2021/158918.

In certain embodiments, a type V-A CRISPR nuclease comprises Moraxella caprae Cpf1 (McCpf1) or a variant thereof. In certain embodiments, a type V-A Cas protein comprises an amino acid sequence at least 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 9 of International (PCT) Application Publication No. WO 2021/158918. In certain embodiments, a type V-A Cas protein comprises the amino acid sequence set forth in SEQ ID NO: 9 of International (PCT) Application Publication No. WO 2021/158918.

In certain embodiments, a type V-A CRISPR nuclease comprises Lachnospiraceae bacterium COE1 Cpf1 (Lb3Cpf1) or a variant thereof. In certain embodiments, a type V-A Cas protein comprises an amino acid sequence at least 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 10 of International (PCT) Application Publication No. WO 2021158918. In certain embodiments, a type V-A Cas protein comprises the amino acid sequence set forth in SEQ ID NO: 10 of International (PCT) Application Publication No. WO 2021/158918.

In certain embodiments, a type V-A CRISPR nuclease comprises Eubacterium coprostanoligenes Cpf1 (EcCpf1) or a variant thereof. In certain embodiments, a type V-A Cas protein comprises an amino acid sequence at least 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence set forth in SEQ ID NO: 11 of International (PCT) Application Publication No. WO 2021158918. In certain embodiments, a type V-A Cas protein comprises the amino acid sequence set forth in SEQ ID NO: 11 of International (PCT) Application Publication No. WO 2021/158918.

In certain embodiments, a type V-A CRISPR nuclease is not Cpf1. In certain embodiments, a type V-A CRISPR nuclease is not AsCpf1.

In certain embodiments, a type V-A CRISPR nuclease comprises a Type V-A nuclease described in U.S. Pat. No. 9,982,279.

In certain embodiments, a Type VA CRISPR nuclease polypeptide used in compositions and methods herein can be represented by a polypeptide that includes a sequence that has at least 60, 70, 80, 85, 90, 95, 96, 97, 98, 99, or 100% sequence identity, preferably at least 80%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% sequence identity with SEQ ID NO: 1 SEQ ID NO: 1 wherein the Type VA CRISPR nuclease polypeptide further comprises at least one, two, three, four, five or six nuclear localization sequences (NLS), each of which can be at or near the amino end or carboxy end of the CRISPR nuclease polypeptide; and/or one or more purification tags; in addition, a cleavage sequence can be provided to remove portions of a protopeptide. As used herein, the term “at or near” an N-terminus or a C-terminus includes where the nearest amino acid of the NLS to the N- or C-terminus is within 300 amino acids, in some cases within 200 amino acids, from the N- or C-terminus of the polypeptide (e.g., a core polypeptide such as one of the CRISPR nucleases described herein, to which the NLS or NLSs is attached). In certain embodiments, a Type V CRISPR nuclease polypeptide, e.g., Type Va CRISPR polypeptide, comprises two, three, four, or five NLSs, each of which are at or near the N-terminus or the C-terminus of the polypeptide, in preferred embodiments the NLSs are at or near the N-terminus. In certain embodiments, a CRISPR nuclease polypeptide, including one or more NLSs and, in some cases, a purification tag and/or a cleavage site, comprises a sequence at least 60, 70, 80, 85, 90, 95, 98, 99%, or 100%, identical, preferably at least 80%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% identical to any one of SEQ ID NOs: 109-112. In certain embodiments, a Type V, e.g., VA CRISPR nuclease polypeptide comprises at least 1-30, 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 2-30, 2-20, 2-15, 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 3-30, 3-20, 3-15, 3-10, 3-9, 3-8, 3-7, 3-6, or 3-5, preferably 1-10, more preferably 2-10, even more preferably 3-10 NLSs, each of which is at or near the N-terminus or the C-terminus of the polypeptide, in preferred embodiments at or near the N-terminus. In certain embodiments, at least two, or at least three, of the NLSs have different mechanisms, that is, different mechanisms by which they localize an attached polypeptide to a nucleus. Such mechanisms are well-known in the art; see, e.g., Lu et al. Cell Commun Signal (2021) 19:60 https://doi.org/10.1186/s12964-021-00741-y. Suitable NLS, purification tag, and cleavage site sequences can be as described elsewhere herein, e.g., in sections labeled Nuclear Localization Signals, Purification Tags, and Cleavage Sites.

SEQ ID NO: 1 MNNGTNNFQNFIGISSLQKTLRNALIPTETTQQFIVKNGIIKEDELRGEN RQILKDIMDDYYRGFISETLSSIDDIDWTSLFEKMEIQLKNGDNKDTLIK EQTEYRKAIHKKFANDDRFKNMFSAKLISDILPEFVIHNNNYSASEKEEK TQVIKLFSRFATSFKDYFKNRANCFSADDISSSSCHRIVNDNAEIFFSNA LVYRRIVKSLSNDDINKISGDMKDSLKEMSLEEIYSYEKYGEFITQEGIS FYNDICGKVNSFMNLYCQKNKENKNLYKLQKLHKQILCIADTSYEVPYKF ESDEEVYQSVNGFLDNISSKHIVERLRKIGDNYNGYNLDKIYIVSKFYES VSQKTYRDWETINTALEIHYNNILPGNGKSKADKVKKAVKNDLQKSITEI NELVSNYKLCSDDNIKAETYIHEISHILNNFEAQELKYNPEIHLVESELK ASELKNVLDVIMNAFHWCSVFMTEELVDKDNNFYAELEEIYDEIYPVISL YNLVRNYVTQKPYSTKKIKLNFGIPTLADGWSKSKEYSNNAIILMRDNLY YLGIFNAKNKPDKKIIEGNTSENKGDYKKMIYNLLPGPNKMIPKVFLSSK TGVETYKPSAYILEGYKQNKHIKSSKDFDITFCHDLIDYFKNCIAIHPEW KNFGFDFSDTSTYEDISGFYREVELQGYKIDWTYISEKDIDLLQEKGQLY LFQIYNKDFSKKSTGNDNLHTMYLKNLFSEENLKDIVLKLNGEAEIFFRK SSIKNPIIHKKGSILVNRTYEAEEKDQFGNIQIVRKNIPENIYQELYKYF NDKSDKELSDEAAKLKNVVGHHEAATNIVKDYRYTYDKYFLHMPITINFK ANKTGFINDRILQYIAKEKDLHVIGIDRGERNLIYVSVIDTCGNIVEQKS FNIVNGYDYQIKLKQQEGARQIARKEWKEIGKIKEIKEGYLSLVIHEISK MVIKYNAIIAMEDLSYGFKKGRFKVERQVYQKFETMLINKLNYLVFKDIS ITENGGLLKGYQLTYIPDKLKNVGHQCGCIFYVPAAYTSKIDPTTGFVNI FKFKDLTVDAKREFIKKFDSIRYDSEKNLFCFTFDYNNFITQNTVMSKSS WSVYTYGVRIKRRFVNGRFSNESDTIDITKDMEKTLEMTDINWRDGHDLR QDIIDYEIVQHIFEIFRLTVQMRNSLSELEDRDYDRLISPVLNENNIFYD SAKAGDALPKDADANGAYCIALKGLYEIKQITENWKEDGKFSRDKLKISN KDWFDFIQNKRYL

Nucleotide sequences coding for SEQ ID NO: 1 can include sequences with less than 99, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, or 40% sequence identity with SEQ ID NO: 22, in preferred embodiments less than 75% sequence identity. In certain embodiments, a nucleotide sequence coding for SEQ ID NO: 1 can also include nucleic acid sequences coding for one or more NLS at the N-terminus and/or C-terminus, as described herein, and/or a tag such as a purification tag at the N-terminus, as described herein. In certain embodiments, provided herein are compositions comprising a first polynucleotide coding for a polypeptide comprising a nucleic acid-guided nuclease comprising a CRISPR Type V nuclease polypeptide, wherein the polynucleotide has less than 75% sequence identity to SEQ ID NO: 22, such as wherein the nuclease polypeptide comprises at least 1, 2, 3, 4, or 5 NLSs, wherein each of the NLSs is at or near the N-terminus or the C-terminus of the nuclease polypeptide. NLSs can be any of those described herein. The first polynucleotide can comprise a sequence coding for a purification tag, such as a purification tag described herein, and/or cleavage site, such as a cleavage site described herein. In certain embodiments the first polynucleotide codes for a polypeptide comprising a sequence at least 60, 70, 80, 85, 90, 95, 98, 99%, or 100%, identical, preferably at least 80%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% identical to any one of SEQ ID NOs: 109-112, such as SEQ ID NO: 109, or SEQ ID NO: 110, or SEQ ID NO: 111, or SEQ ID NO: 112. the first polynucleotide comprises a sequence at least 50, 60, 70, 80, 90, 95, 97, or 99% identical, or 100% identical, preferably at least 80%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% identical to SEQ ID NO: 113. In certain embodiment the composition further comprises a second polynucleotide coding for a gNA or portion thereof, wherein the gNA, e.g., gRNA, comprises a spacer sequence that targets a target nucleotide sequence within a polynucleotide, or a polynucleotide coding for the gNA, e.g., gRNA, wherein the gNA, e.g., gRNA is compatible with the Type V CRISPR nuclease. In certain embodiments the first and second polynucleotides are the same. The composition can further comprise a third polynucleotide comprising a donor template. In certain embodiments, provided is a vector comprising one of the polynucleotide compositions of this paragraph. In certain embodiments, provided is a cell comprising one of the polynucleotide compositions of this paragraph, e.g., a human cell, such as an immune cell, for example a T cell, or a stem cell, such as an iPSC. In certain embodiments, provided is a method comprising inserting any one of the polynucleotide compositions of this paragraph into a cell. In certain embodiments inserting the composition comprises electroporation.

SEQ ID NO: 22: ATGAACAACGGCACAAATAATTTTCAGAACTTCATCGGGATCTCAAGTTTGCAGAAA ACGCTGCGCAATGCTCTGATCCCCACGGAAACCACGCAACAGTTCATCGTCAAGAA CGGAATAATTAAAGAAGATGAGTTACGTGGCGAGAACCGCCAGATTCTGAAAGATA TCATGGATGACTACTACCGCGGATTCATCTCTGAGACTCTGAGTTCTATTGATGACA TAGATTGGACTAGCCTGTTCGAAAAAATGGAAATTCAGCTGAAAAATGGTGATAAT AAAGATACCTTAATTAAGGAACAGACAGAGTATCGGAAAGCAATCCATAAAAAATT TGCGAACGACGATCGGTTTAAGAACATGTTTAGCGCCAAACTGATTAGTGACATATT ACCTGAATTTGTCATCCACAACAATAATTATTCGGCATCAGAGAAAGAGGAAAAAA CCCAGGTGATAAAATTGTTTTCGCGCTTTGCGACTAGCTTTAAAGATTACTTCAAGA ACCGTGCAAATTGCTTTTCAGCGGACGATATTTCATCAAGCAGCTGCCATCGCATCG TCAACGACAATGCAGAGATATTCTTTTCAAATGCGCTGGTCTACCGCCGGATCGTAA AATCGCTGAGCAATGACGATATCAACAAAATTTCGGGCGATATGAAAGATTCATTA AAAGAAATGAGTCTGGAAGAAATATATTCTTACGAGAAGTATGGGGAATTTATTAC CCAGGAAGGCATTAGCTTCTATAATGATATCTGTGGGAAAGTGAATTCTTTTATGAA CCTGTATTGTCAGAAAAATAAAGAAAACAAAAATTTATACAAACTTCAGAAACTTC ACAAACAGATTCTATGCATTGCGGACACTAGCTATGAGGTCCCGTATAAATTTGAAA GTGACGAGGAAGTGTACCAATCAGTTAACGGCTTCCTTGATAACATTAGCAGCAAA CATATAGTCGAAAGATTACGCAAAATCGGCGATAACTATAACGGCTACAACCTGGA TAAAATTTATATCGTGTCCAAATTTTACGAGAGCGTTAGCCAAAAAACCTACCGCGA CTGGGAAACAATTAATACCGCCCTCGAAATTCATTACAATAATATCTTGCCGGGTAA CGGTAAAAGTAAAGCCGACAAAGTAAAAAAAGCGGTTAAGAATGATTTACAGAAAT CCATCACCGAAATAAATGAACTAGTGTCAAACTATAAGCTGTGCAGTGACGACAAC ATCAAAGCGGAGACTTATATACATGAGATTAGCCATATCTTGAATAACTTTGAAGCA CAGGAATTGAAATACAATCCGGAAATTCACCTAGTTGAATCCGAGCTCAAAGCGAG TGAGCTTAAAAACGTGCTGGACGTGATCATGAATGCGTTTCATTGGTGTTCGGTTTTT ATGACTGAGGAACTTGTTGATAAAGACAACAATTTTTATGCGGAACTGGAGGAGAT TTACGATGAAATTTATCCAGTAATTAGTCTGTACAACCTGGTTCGTAACTACGTTACC CAGAAACCGTACAGCACGAAAAAGATTAAATTGAACTTTGGAATACCGACGTTAGC AGACGGTTGGTCAAAGTCCAAAGAGTATTCTAATAACGCTATCATACTGATGCGCGA CAATCTGTATTATCTGGGCATCTTTAATGCGAAGAATAAACCGGACAAGAAGATTAT CGAGGGTAATACGTCAGAAAATAAGGGTGACTACAAAAAGATGATTTATAATTTGC TCCCGGGTCCCAACAAAATGATCCCGAAAGTTTTCTTGAGCAGCAAGACGGGGGTG GAAACGTATAAACCGAGCGCCTATATCCTAGAGGGGTATAAACAGAATAAACATAT CAAGTCTTCAAAAGACTTTGATATCACTTTCTGTCATGATCTGATCGACTACTTCAAA AACTGTATTGCAATTCATCCCGAGTGGAAAAACTTCGGTTTTGATTTTAGCGACACC AGTACTTATGAAGACATTTCCGGGTTTTATCGTGAGGTAGAGTTACAAGGTTACAAG ATTGATTGGACATACATTAGCGAAAAAGACATTGATCTGCTGCAGGAAAAAGGTCA ACTGTATCTGTTCCAGATATATAACAAAGATTTTTCGAAAAAATCAACCGGGAATGA CAACCTTCACACCATGTACCTGAAAAATCTTTTCTCAGAAGAAAATCTTAAGGATAT CGTCCTGAAACTTAACGGCGAAGCGGAAATCTTCTTCAGGAAGAGCAGCATAAAGA ACCCAATCATTCATAAAAAAGGCTCGATTTTAGTCAACCGTACCTACGAAGCAGAA GAAAAAGACCAGTTTGGCAACATTCAAATTGTGCGTAAAAATATTCCGGAAAACAT TTATCAGGAGCTGTACAAATACTTCAACGATAAAAGCGACAAAGAGCTGTCTGATG AAGCAGCCAAACTGAAGAATGTAGTGGGACACCACGAGGCAGCGACGAATATAGTC AAGGACTATCGCTACACGTATGATAAATACTTCCTTCATATGCCTATTACGATCAAT TTCAAAGCCAATAAAACGGGTTTTATTAATGATAGGATCTTACAGTATATCGCTAAA GAAAAAGACTTACATGTGATCGGCATTGATCGGGGCGAGCGTAACCTGATCTACGT GTCCGTGATTGATACTTGTGGTAATATAGTTGAACAGAAAAGCTTTAACATTGTAAA CGGCTACGACTATCAGATAAAACTGAAACAACAGGAGGGCGCTAGACAGATTGCGC GGAAAGAATGGAAAGAAATTGGTAAAATTAAAGAGATCAAAGAGGGCTACCTGAG CTTAGTAATCCACGAGATCTCTAAAATGGTAATCAAATACAATGCAATTATAGCGAT GGAGGATTTGTCTTATGGTTTTAAAAAAGGGCGCTTTAAGGTCGAACGGCAAGTTTA CCAGAAATTTGAAACCATGCTCATCAATAAACTCAACTATCTGGTATTTAAAGATAT TTCGATTACCGAGAATGGCGGTCTCCTGAAAGGTTATCAGCTGACATACATTCCTGA TAAACTTAAAAACGTGGGTCATCAGTGCGGCTGCATTTTTTATGTGCCTGCTGCATA CACGAGCAAAATTGATCCGACCACCGGCTTTGTGAATATCTTTAAATTTAAAGACCT GACAGTGGACGCAAAACGTGAATTCATTAAAAAATTTGACTCAATTCGTTATGACAG TGAAAAAAATCTGTTCTGCTTTACATTTGACTACAATAACTTTATTACGCAAAACAC GGTCATGAGCAAATCATCGTGGAGTGTGTATACATACGGCGTGCGCATCAAACGTC GCTTTGTGAACGGCCGCTTCTCAAACGAAAGTGATACCATTGACATAACCAAAGATA TGGAGAAAACGTTGGAAATGACGGACATTAACTGGCGCGATGGCCACGATCTTCGT CAAGACATTATAGATTATGAAATTGTTCAGCACATATTCGAAATTTTCCGTTTAACA GTGCAAATGCGTAACTCCTTGTCTGAACTGGAGGACCGTGATTACGATCGTCTCATT TCACCTGTACTGAACGAAAATAACATTTTTTATGACAGCGCGAAAGCGGGGGATGC ACTTCCTAAGGATGCCGATGCAAATGGTGCGTATTGTATTGCATTAAAAGGGTTATA TGAAATTAAACAAATTACCGAAAATTGGAAAGAAGATGGTAAATTTTCGCGCGATA AACTCAAAATCAGCAATAAAGATTGGTTCGACTTTATCCAGAATAAGCGCTATCTCT AA

Exemplary nucleotide sequences coding for SEQ ID NO: 1 can include, e.g., SEQ ID NOs: 23-42:

SEQ ID NO: 23 ATGAACAACGGAACAAATAATTTTCAGAACTTTATTGGGATCAGTTCGCTTCAGAAA ACGCTTCGTAATGCTCTGATTCCCACAGAAACCACTCAGCAGTTTATCGTAAAGAAT GGCATTATCAAGGAGGATGAATTACGCGGCGAGAACCGCCAAATCTTAAAAGATAT CATGGACGACTACTACCGCGGTTTCATTAGCGAAACTCTTAGTTCAATTGACGACAT TGACTGGACGTCCTTGTTCGAAAAGATGGAGATTCAATTAAAGAACGGTGATAACA AGGATACGTTGATTAAAGAACAGACGGAGTACCGTAAGGCTATCCACAAAAAATTT GCAAACGACGACCGCTTTAAAAATATGTTTAGCGCAAAATTAATCTCCGACATCCTG CCTGAATTCGTCATCCATAACAATAACTATAGCGCCTCGGAAAAAGAAGAAAAAAC GCAGGTTATTAAACTTTTCTCGCGCTTTGCAACAAGCTTTAAGGATTACTTCAAAAA TCGCGCCAATTGTTTTTCAGCCGACGACATTAGCTCCAGTTCCTGCCACCGTATTGTG AATGACAACGCTGAGATTTTTTTTTCCAATGCGCTGGTTTATCGTCGTATTGTTAAGA GCCTTAGTAACGACGACATTAATAAAATTAGCGGTGATATGAAGGATAGCTTGAAA GAAATGAGTCTGGAAGAGATCTATAGTTACGAGAAGTACGGCGAATTTATTACCCA GGAGGGCATTTCATTTTACAATGATATCTGTGGAAAAGTCAACTCCTTTATGAACTT GTATTGCCAAAAGAATAAAGAAAACAAAAACCTGTACAAACTGCAAAAGTTACACA AGCAGATTTTGTGTATCGCAGACACGTCATACGAAGTACCGTACAAGTTTGAGTCCG ATGAAGAAGTGTACCAAAGCGTTAATGGCTTTTTGGATAACATTTCGAGCAAACATA TCGTAGAGCGTTTGCGTAAGATTGGTGATAATTACAACGGTTACAATTTAGACAAAA TCTATATCGTCTCTAAGTTTTACGAAAGTGTTTCTCAGAAAACTTACCGCGATTGGG AGACGATCAACACTGCGCTGGAGATTCATTACAATAATATCCTTCCAGGTAACGGTA AAAGCAAAGCTGATAAGGTGAAAAAGGCGGTTAAAAATGACCTTCAAAAGTCTATC ACAGAAATCAACGAATTGGTCAGCAATTATAAGCTTTGCAGTGACGATAACATTAA GGCCGAGACTTACATCCATGAGATCTCTCACATTCTTAATAATTTTGAAGCGCAAGA GCTGAAATACAATCCTGAAATCCATCTGGTCGAAAGTGAATTAAAAGCCTCCGAATT AAAAAATGTCTTGGACGTGATCATGAATGCGTTCCATTGGTGCTCAGTTTTTATGAC GGAAGAGTTGGTGGACAAAGACAACAATTTTTACGCCGAGCTTGAGGAAATTTACG ACGAAATTTACCCCGTTATTTCGTTATACAACCTTGTGCGTAATTACGTTACACAAA AGCCCTATTCGACAAAGAAAATCAAGTTAAATTTCGGGATTCCCACATTAGCTGATG GATGGTCCAAATCCAAAGAATACTCGAATAACGCTATCATCCTTATGCGTGATAATT TGTACTACTTAGGCATCTTCAATGCGAAGAACAAACCTGACAAGAAAATTATCGAA GGAAACACTTCGGAGAACAAAGGTGATTATAAAAAGATGATCTACAACTTGCTTCC CGGGCCAAACAAAATGATTCCCAAGGTATTTTTGAGTTCTAAAACCGGTGTCGAAAC TTACAAACCAAGTGCTTATATTTTGGAAGGATACAAACAGAACAAACATATCAAGT CTTCGAAAGACTTCGATATTACGTTCTGCCACGATCTGATCGATTACTTCAAGAACT GTATTGCTATTCACCCCGAGTGGAAGAACTTTGGATTTGATTTCTCCGACACGTCCA CTTATGAAGATATCTCTGGCTTCTATCGCGAGGTTGAATTACAAGGGTATAAGATTG ACTGGACTTATATTTCGGAGAAGGATATCGATCTTTTGCAAGAAAAAGGGCAACTTT ATTTATTTCAGATCTATAACAAGGACTTTTCAAAAAAGAGCACTGGAAATGACAATC TGCATACCATGTACCTTAAGAACCTGTTCTCGGAAGAGAACCTGAAGGACATTGTAC TTAAACTGAATGGAGAGGCAGAGATCTTCTTTCGCAAATCAAGCATTAAGAACCCA ATTATTCACAAAAAGGGGAGTATCTTAGTAAATCGCACATATGAGGCTGAGGAAAA AGATCAGTTTGGTAACATTCAGATCGTGCGTAAGAACATTCCTGAAAATATCTATCA GGAACTTTATAAGTATTTCAACGATAAAAGTGATAAAGAGCTGAGTGACGAAGCGG CTAAACTTAAGAATGTTGTGGGACACCATGAGGCAGCAACCAATATTGTGAAGGAT TATCGCTATACGTACGACAAATACTTTTTACACATGCCCATCACTATTAATTTTAAAG CTAATAAGACTGGCTTCATTAACGATCGCATCCTGCAGTACATTGCTAAGGAAAAGG ATCTTCACGTTATCGGTATCGATCGCGGGGAGCGTAATCTTATCTACGTCTCTGTCAT TGACACGTGTGGCAATATTGTGGAGCAAAAGTCCTTCAATATTGTTAACGGCTATGA CTATCAGATTAAATTGAAACAGCAGGAAGGTGCGCGTCAGATTGCCCGCAAGGAAT GGAAGGAAATTGGCAAGATCAAAGAAATTAAGGAGGGCTACTTAAGCTTAGTAATT CACGAAATTAGTAAAATGGTTATCAAATACAACGCCATCATCGCGATGGAGGATCTT TCGTACGGGTTTAAGAAAGGTCGTTTTAAAGTGGAGCGTCAGGTGTACCAGAAATTT GAAACTATGCTTATTAACAAACTTAACTACCTGGTTTTCAAGGATATCAGTATTACT GAAAACGGGGGGCTGTTAAAAGGGTATCAATTAACTTACATTCCAGACAAATTAAA GAACGTTGGACATCAGTGTGGCTGCATTTTTTATGTACCAGCTGCATACACTTCAAA GATCGATCCTACGACTGGGTTCGTGAACATTTTTAAGTTTAAAGACTTGACGGTAGA TGCCAAGCGCGAATTCATCAAGAAATTCGACAGCATTCGCTACGACTCTGAGAAAA ATCTTTTCTGTTTCACATTCGATTATAACAATTTCATTACGCAGAACACAGTAATGTC CAAGTCTTCTTGGAGTGTTTATACATATGGTGTCCGCATTAAGCGCCGTTTCGTCAAC GGCCGCTTCAGTAATGAGAGCGATACTATTGACATCACAAAAGACATGGAAAAAAC ACTGGAAATGACCGACATCAATTGGCGTGACGGCCATGACTTACGTCAGGATATCAT TGATTATGAGATCGTTCAACACATCTTCGAAATCTTTCGCTTGACTGTTCAAATGCGC AATTCCTTGTCGGAATTGGAGGACCGTGATTATGACCGCTTAATTTCCCCCGTCTTAA ATGAAAACAATATTTTTTATGACTCTGCAAAAGCTGGAGATGCTCTGCCGAAAGACG CCGATGCAAATGGGGCATATTGCATTGCTTTAAAGGGGCTTTACGAGATCAAGCAA ATCACCGAAAACTGGAAAGAGGATGGAAAGTTTTCGCGTGATAAACTGAAGATCTC TAACAAAGACTGGTTCGACTTTATCCAGAACAAGCGTTATTT SEQ ID NO: 24 ATGAACAACGGCACCAATAACTTCCAAAACTTCATCGGGATCTCTAGCCTTCAGAAG ACGCTTCGCAATGCTCTTATCCCAACTGAGACCACTCAACAATTTATTGTGAAGAAT GGAATTATTAAAGAGGACGAACTGCGTGGCGAGAATCGTCAGATCTTAAAGGACAT TATGGATGATTATTACCGTGGATTCATCTCCGAAACATTATCGTCGATCGATGATAT CGATTGGACTTCTCTGTTCGAGAAAATGGAAATTCAATTGAAAAACGGAGATAATA AAGATACGCTTATCAAAGAACAGACGGAATATCGTAAAGCGATTCATAAGAAATTC GCAAATGACGATCGTTTCAAAAATATGTTCAGTGCCAAGCTTATTTCGGACATTTTA CCTGAATTTGTAATTCATAATAATAACTACTCAGCAAGTGAGAAGGAGGAGAAAAC CCAAGTTATTAAACTGTTCTCTCGTTTCGCAACGTCCTTTAAAGATTACTTTAAAAAC CGCGCGAATTGCTTTAGCGCTGACGACATTTCCAGCTCATCCTGTCATCGCATCGTA AACGACAATGCGGAAATCTTCTTCAGCAACGCCCTGGTTTACCGCCGCATCGTCAAA AGCTTATCGAATGACGACATCAATAAGATCTCAGGAGATATGAAGGACTCGCTTAA GGAGATGTCTCTGGAGGAAATTTATAGTTACGAAAAGTATGGAGAGTTCATTACCCA GGAGGGAATCTCGTTCTACAATGACATTTGCGGGAAGGTGAACTCCTTCATGAACTT ATACTGCCAGAAAAACAAAGAGAACAAAAATCTGTATAAATTGCAGAAATTACATA AACAGATTCTTTGTATTGCTGACACTTCCTACGAAGTACCCTATAAATTCGAGTCAG ATGAAGAAGTATACCAGTCCGTGAACGGATTTCTGGACAATATCTCCTCAAAACACA TCGTGGAACGCTTACGTAAAATTGGCGATAATTATAATGGTTACAATCTTGACAAAA TTTATATCGTATCTAAATTTTACGAGAGTGTGAGCCAAAAGACCTACCGCGACTGGG AGACCATCAACACAGCTTTAGAAATTCACTATAATAATATCTTACCCGGCAATGGTA AGAGCAAGGCTGACAAGGTAAAAAAGGCCGTCAAGAATGATTTGCAGAAATCTATT ACAGAAATTAATGAGTTAGTCTCCAACTATAAGCTTTGTTCCGACGATAACATCAAA GCTGAGACATATATTCATGAGATTAGTCACATTCTTAACAACTTCGAGGCCCAGGAA CTTAAGTACAATCCTGAAATTCATCTTGTCGAGTCTGAGCTGAAAGCTAGTGAATTG AAAAATGTTTTAGACGTTATTATGAACGCATTCCACTGGTGCTCTGTGTTTATGACA GAAGAACTGGTCGACAAGGACAATAACTTCTATGCCGAACTTGAGGAAATCTACGA TGAAATTTACCCTGTAATCTCCTTGTATAATCTTGTACGTAATTACGTCACTCAAAAA CCTTACAGCACGAAAAAAATTAAATTGAACTTCGGGATTCCTACACTTGCCGACGGG TGGTCTAAATCCAAGGAATATAGCAACAATGCCATTATTTTAATGCGCGACAATCTT TACTATTTAGGAATTTTTAACGCTAAGAACAAGCCCGATAAAAAGATTATTGAAGGA AACACGTCTGAAAATAAGGGCGACTACAAAAAGATGATTTATAACCTTTTGCCCGGT CCAAACAAAATGATCCCAAAGGTATTCCTGTCATCCAAAACAGGGGTTGAGACATA TAAGCCCAGCGCATATATTCTGGAAGGATACAAACAGAATAAACATATCAAAAGCA GCAAAGATTTTGACATTACTTTTTGCCACGATTTAATCGACTACTTCAAAAACTGTAT CGCTATCCACCCTGAATGGAAGAATTTCGGATTTGATTTCTCAGATACAAGTACGTA TGAGGATATCAGCGGTTTCTATCGCGAAGTTGAACTTCAAGGGTATAAAATTGACTG GACCTACATTAGTGAGAAGGACATCGACCTGTTACAGGAAAAAGGCCAATTGTACT TGTTTCAGATCTACAATAAGGATTTCTCAAAAAAATCGACCGGCAATGATAACTTGC ACACCATGTACCTGAAGAACCTTTTTTCGGAGGAAAACCTTAAAGACATTGTCCTGA AGTTGAATGGAGAAGCGGAGATTTTCTTTCGTAAGTCTTCCATTAAAAATCCAATTA TTCATAAGAAGGGCAGCATCCTTGTGAACCGTACGTACGAGGCGGAAGAGAAGGAC CAATTCGGTAACATTCAAATCGTCCGCAAGAACATCCCTGAAAATATTTATCAGGAG CTTTACAAGTATTTCAATGATAAGTCCGACAAGGAATTATCAGATGAGGCTGCGAAG TTGAAAAATGTTGTTGGTCATCACGAGGCGGCGACGAATATTGTAAAGGATTATCGC TACACTTATGACAAGTACTTTCTGCACATGCCGATCACCATTAATTTCAAGGCGAAC AAAACAGGATTTATTAATGACCGCATCTTACAATACATTGCCAAAGAAAAGGACTT ACACGTTATTGGCATTGATCGTGGAGAACGCAACTTAATCTACGTAAGCGTTATTGA CACTTGCGGGAATATCGTAGAACAAAAGAGCTTCAACATCGTGAATGGTTACGATT ACCAGATCAAGCTTAAGCAGCAGGAGGGAGCGCGCCAGATCGCGCGCAAGGAATG GAAGGAGATTGGTAAGATCAAGGAAATCAAGGAAGGTTATCTGTCCTTGGTAATCC ACGAAATTTCGAAAATGGTTATCAAATACAATGCTATTATTGCAATGGAGGACTTGT CCTACGGCTTTAAAAAAGGACGCTTTAAGGTGGAGCGCCAGGTTTATCAAAAGTTTG AAACAATGCTGATTAACAAGCTGAACTATTTGGTCTTTAAAGATATCTCCATCACCG AAAATGGTGGGCTTTTGAAAGGCTATCAACTTACATATATCCCTGATAAGCTTAAGA ATGTGGGTCATCAGTGCGGGTGCATTTTTTATGTTCCTGCAGCCTACACGTCCAAAA TCGATCCTACAACTGGATTTGTTAATATCTTCAAATTTAAGGATCTTACCGTCGACGC GAAGCGCGAATTTATCAAGAAATTCGATAGTATTCGTTATGATTCCGAAAAAAACCT TTTCTGTTTCACCTTTGATTATAATAACTTTATCACGCAAAATACTGTCATGAGCAAA TCGAGTTGGTCTGTGTACACTTACGGAGTACGCATCAAGCGTCGTTTTGTTAATGGG CGCTTCAGTAACGAGTCAGACACGATTGATATCACAAAAGATATGGAGAAAACGCT GGAGATGACAGACATCAATTGGCGCGATGGTCATGACTTACGTCAAGACATTATCG ATTATGAAATTGTCCAGCATATCTTTGAGATCTTTCGTTTGACTGTTCAGATGCGCAA CAGCCTGTCAGAATTGGAGGATCGTGACTATGATCGCCTTATTTCTCCCGTCTTAAAT GAGAACAATATCTTCTACGACTCAGCCAAGGCTGGAGATGCACTGCCAAAAGACGC CGACGCAAATGGGGCCTACTGTATTGCATTGAAGGGGTTGTACGAGATCAAACAGA TTACAGAAAATTGGAAGGAGGACGGTAAGTTCTCTCGTGATAAGCTGAAGATTTCTA ACAAAGACTGGTTCGATTTCATTCAGAACAAACGTTACCTG SEQ ID NO: 25 ATGAACAACGGTACCAATAACTTTCAGAATTTCATTGGAATCAGCAGCTTACAGAAA ACCCTGCGCAATGCACTTATCCCCACTGAGACAACCCAGCAGTTCATTGTAAAGAAC GGGATTATTAAAGAAGATGAGCTTCGCGGGGAGAATCGTCAGATCTTAAAGGATAT TATGGACGATTACTACCGTGGCTTCATTTCGGAGACGCTGTCGTCGATCGACGACAT CGACTGGACATCCTTGTTTGAAAAGATGGAAATCCAACTGAAGAATGGCGATAACA AGGACACGTTAATCAAAGAGCAGACGGAATACCGTAAAGCTATCCACAAAAAGTTC GCTAATGACGACCGCTTTAAGAACATGTTCTCAGCAAAACTTATTAGCGATATTTTA CCTGAATTTGTCATCCACAATAACAATTACTCCGCGAGTGAAAAAGAGGAGAAAAC CCAGGTGATTAAGCTGTTTTCCCGTTTTGCAACCAGTTTCAAGGACTATTTTAAGAAT CGTGCTAATTGTTTCTCTGCAGACGACATTTCCTCGTCGTCCTGCCATCGCATTGTTA ATGATAATGCTGAAATCTTTTTTTCAAACGCACTTGTGTATCGTCGCATTGTCAAAAG CTTAAGTAATGACGATATCAATAAGATCTCAGGAGACATGAAGGACTCCCTGAAAG AAATGTCATTGGAAGAAATTTACTCTTATGAAAAGTATGGAGAATTTATTACGCAGG AGGGTATCAGCTTCTATAACGACATTTGTGGTAAAGTGAACAGCTTTATGAATCTTT ATTGTCAAAAGAATAAAGAGAACAAAAATCTGTACAAGCTGCAGAAATTGCATAAA CAAATTCTGTGCATTGCAGATACTTCGTATGAGGTTCCTTACAAATTCGAGTCGGAT GAGGAGGTGTATCAAAGCGTAAACGGATTTTTGGATAACATTAGTAGTAAGCATATT GTGGAACGCCTTCGCAAGATTGGTGACAACTATAACGGATACAACTTAGACAAGAT CTATATTGTCTCGAAGTTTTACGAAAGTGTTTCCCAAAAGACTTATCGCGACTGGGA GACAATCAACACTGCGCTGGAAATTCACTATAACAATATCTTGCCGGGGAACGGAA AAAGTAAGGCAGATAAGGTGAAGAAAGCAGTCAAAAATGATCTGCAAAAAAGCAT TACTGAAATTAACGAACTTGTGTCAAATTACAAATTGTGTTCGGATGACAATATTAA AGCGGAAACGTATATCCACGAGATCTCGCACATTCTTAATAATTTCGAGGCGCAGGA ATTAAAGTATAATCCTGAGATCCATTTGGTGGAATCAGAACTTAAAGCTAGTGAACT GAAAAATGTCCTGGACGTTATTATGAATGCATTTCACTGGTGTTCTGTCTTTATGACA GAAGAACTTGTCGACAAAGACAACAACTTTTATGCGGAATTAGAAGAGATTTACGA CGAAATTTATCCCGTTATTTCGTTATATAATTTAGTTCGTAATTACGTGACTCAGAAA CCCTACAGCACAAAAAAGATTAAATTAAACTTTGGGATTCCGACTCTTGCTGATGGA TGGAGCAAGTCCAAGGAGTACTCTAATAACGCCATTATCTTGATGCGTGACAACCTG TACTACCTGGGCATTTTTAACGCTAAAAACAAACCCGACAAAAAGATCATTGAAGG GAACACCTCGGAAAATAAGGGGGACTATAAAAAAATGATCTACAATCTGTTGCCAG GCCCAAATAAGATGATCCCAAAGGTTTTTTTATCTTCCAAAACTGGCGTAGAAACTT ACAAGCCGAGCGCATACATCCTTGAAGGATATAAACAAAACAAACATATCAAAAGT TCAAAGGACTTCGATATTACGTTCTGCCATGATTTAATCGATTATTTCAAGAATTGCA TCGCGATTCACCCAGAGTGGAAAAACTTTGGGTTTGATTTTTCAGACACCAGCACTT ACGAGGATATTAGTGGATTCTATCGTGAGGTTGAACTGCAGGGCTATAAAATTGACT GGACCTATATTTCTGAAAAAGATATTGATCTGCTTCAGGAGAAAGGCCAATTGTACT TATTTCAAATCTATAACAAGGATTTCTCCAAGAAGTCCACGGGTAATGACAACTTAC ACACAATGTATCTGAAGAATCTGTTTAGTGAGGAGAACTTGAAGGACATTGTGCTGA AGCTTAATGGCGAGGCCGAAATCTTTTTTCGTAAGTCCTCCATTAAAAACCCTATTA TCCATAAGAAAGGGAGTATTCTTGTCAACCGCACGTATGAGGCCGAAGAAAAGGAC CAATTCGGAAACATCCAAATTGTCCGTAAAAATATTCCTGAGAACATTTACCAGGAG CTTTACAAGTATTTCAACGACAAGAGTGATAAAGAACTTTCAGATGAGGCGGCGAA ACTGAAGAATGTAGTGGGGCACCACGAAGCTGCCACGAATATTGTAAAGGATTACC GTTACACCTACGACAAGTACTTTTTGCATATGCCCATCACAATTAATTTTAAGGCCA ATAAAACTGGTTTTATCAACGATCGTATCTTACAGTACATTGCTAAGGAAAAAGATC TGCACGTTATCGGTATCGATCGCGGGGAACGCAATCTGATTTATGTTAGTGTGATTG ACACGTGCGGAAATATTGTTGAGCAGAAGAGCTTTAATATCGTAAATGGATATGACT ATCAAATTAAACTGAAGCAACAGGAAGGGGCCCGCCAGATTGCCCGCAAGGAGTGG AAAGAAATTGGAAAGATCAAGGAGATTAAAGAAGGGTACCTTTCCCTTGTTATCCA CGAAATCTCGAAAATGGTGATCAAGTACAATGCCATTATTGCTATGGAGGATCTGTC ATATGGGTTTAAGAAAGGCCGCTTTAAGGTGGAACGTCAGGTTTACCAGAAGTTTGA GACCATGCTTATCAATAAGCTGAATTATCTTGTCTTCAAAGACATCTCAATCACAGA GAACGGCGGGCTGTTAAAAGGATATCAGCTGACCTATATCCCCGACAAACTGAAAA ATGTCGGGCACCAATGCGGCTGTATTTTCTACGTGCCCGCTGCATACACATCTAAAA TTGACCCAACGACTGGATTCGTAAATATTTTTAAGTTTAAGGATCTTACGGTAGATG CAAAGCGCGAATTTATCAAGAAATTTGATAGTATCCGTTACGACAGCGAGAAAAAC TTATTTTGTTTTACGTTCGATTATAACAACTTCATCACGCAAAATACCGTCATGTCAA AATCTTCCTGGTCAGTCTATACGTATGGCGTCCGTATCAAGCGCCGCTTCGTCAACG GGCGTTTTTCAAACGAGTCAGATACCATCGATATCACCAAAGATATGGAAAAAACA TTGGAGATGACGGACATCAATTGGCGCGATGGTCATGACTTACGCCAGGACATTATT GACTACGAAATCGTACAACATATTTTTGAGATTTTCCGTCTGACCGTGCAAATGCGC AACTCATTATCCGAACTTGAGGATCGTGATTACGACCGCTTGATCAGTCCTGTTCTG AACGAGAATAATATTTTTTACGACAGTGCCAAGGCGGGAGACGCACTGCCCAAGGA CGCTGACGCTAACGGAGCTTATTGTATTGCGTTGAAGGGACTTTACGAAATCAAGCA AATCACTGAAAACTGGAAGGAGGATGGTAAATTCTCACGCGACAAGTTGAAAATTT CGAACAAGGACTGGTTCGATTTCATCCAAAACAAGCGTTATTTA SEQ ID NO: 26 ATGAACAACGGGACTAATAACTTCCAGAACTTCATCGGTATTTCATCATTACAAAAA ACGCTTCGTAACGCCTTGATCCCAACAGAAACGACCCAACAATTTATTGTAAAAAAC GGCATCATCAAAGAAGACGAACTGCGTGGCGAAAATCGCCAAATTTTGAAGGACAT TATGGATGACTATTATCGTGGGTTTATCTCGGAGACATTATCCTCCATCGACGACATT GATTGGACGAGTCTTTTTGAGAAAATGGAGATCCAGCTTAAAAATGGTGATAACAA GGATACATTGATCAAGGAGCAAACCGAGTACCGCAAGGCCATCCATAAGAAGTTCG CAAATGACGACCGCTTCAAAAATATGTTTAGTGCCAAATTGATCTCGGATATCCTTC CTGAGTTCGTAATTCACAACAATAATTATAGCGCATCCGAAAAGGAGGAAAAGACT CAAGTCATTAAGCTTTTCAGTCGCTTTGCTACCTCGTTTAAGGACTATTTCAAGAACC GCGCGAACTGCTTCTCAGCGGATGACATTTCTTCCTCGTCGTGTCACCGCATCGTGA ATGATAATGCGGAGATCTTCTTTAGTAATGCCTTGGTATACCGCCGCATTGTTAAAT CCCTGTCTAACGACGATATCAATAAGATCTCAGGAGATATGAAGGATAGCCTTAAA GAAATGTCTCTGGAAGAAATTTACTCCTATGAAAAGTACGGTGAGTTTATCACCCAA GAGGGGATTAGCTTTTATAACGATATCTGCGGGAAGGTGAATTCGTTTATGAACCTT TATTGTCAAAAGAATAAGGAGAATAAGAACTTATATAAGCTTCAGAAACTGCATAA ACAAATCTTATGCATTGCCGATACTAGCTATGAAGTTCCGTATAAATTCGAGAGCGA TGAAGAAGTTTATCAGAGCGTCAATGGGTTCTTGGATAACATTTCATCAAAACACAT CGTGGAACGTCTGCGTAAGATTGGGGATAACTACAACGGATATAATCTTGACAAAA TTTATATTGTATCTAAATTCTATGAGTCGGTGAGTCAAAAGACCTACCGTGATTGGG AAACAATCAATACCGCGTTAGAAATCCACTATAACAACATTCTGCCAGGGAATGGT AAAAGTAAAGCGGACAAAGTCAAGAAGGCTGTGAAGAACGATCTGCAAAAGAGTA TTACAGAGATTAACGAATTAGTCTCCAATTATAAGTTATGCTCGGACGATAACATTA AGGCGGAGACGTATATTCATGAGATTTCGCATATTCTTAACAACTTCGAGGCACAAG AGCTTAAGTATAACCCAGAGATTCACCTTGTCGAATCGGAGCTGAAGGCATCGGAA TTAAAAAATGTCTTAGATGTAATCATGAACGCGTTCCATTGGTGCAGTGTTTTCATG ACTGAGGAGTTAGTTGACAAGGACAATAACTTCTACGCAGAATTAGAAGAGATCTA TGATGAGATTTATCCAGTGATTTCGCTGTATAATCTGGTACGTAATTACGTCACTCAA AAGCCCTACTCAACAAAAAAAATTAAGCTGAACTTCGGAATTCCGACTCTGGCCGA CGGGTGGTCCAAGTCAAAGGAGTATTCTAATAATGCTATCATCCTGATGCGCGATAA CTTATACTATTTGGGAATTTTCAATGCCAAAAATAAACCAGATAAAAAGATTATCGA AGGTAATACAAGCGAGAATAAGGGTGACTATAAGAAAATGATTTACAATCTTCTTC CAGGCCCTAACAAGATGATTCCCAAAGTTTTTTTGTCCAGTAAAACAGGGGTCGAAA CTTACAAGCCCAGTGCCTATATCCTTGAAGGGTACAAGCAGAATAAGCACATCAAA TCCTCGAAAGACTTTGATATTACATTTTGTCATGACTTAATCGATTATTTTAAGAACT GTATCGCAATCCATCCAGAATGGAAGAACTTCGGGTTTGATTTCTCTGATACTTCCA CGTATGAGGATATTTCCGGGTTCTACCGCGAAGTAGAGCTTCAGGGCTATAAAATTG ACTGGACATATATTTCAGAAAAAGACATCGATCTGTTACAAGAAAAAGGACAGTTG TATCTGTTTCAAATCTATAATAAGGATTTCTCCAAAAAGTCAACTGGAAATGATAAC TTACATACAATGTATCTGAAAAATCTTTTTAGTGAAGAGAATTTGAAGGATATCGTG CTGAAGTTAAATGGCGAAGCAGAGATCTTCTTCCGCAAGTCCTCGATCAAGAATCCT ATCATCCACAAGAAAGGTAGTATTCTGGTTAACCGCACGTACGAGGCCGAGGAAAA AGACCAGTTCGGTAATATCCAGATTGTACGTAAGAATATTCCTGAAAATATTTACCA GGAATTATACAAGTATTTTAACGACAAATCGGATAAGGAGCTTTCAGATGAGGCCG CAAAGTTGAAGAACGTCGTAGGACACCATGAGGCCGCTACGAATATCGTCAAGGAC TACCGCTATACGTATGACAAGTACTTCCTGCACATGCCTATTACTATCAATTTCAAA GCTAATAAAACAGGATTCATCAATGATCGTATCCTTCAGTACATTGCCAAAGAAAAA GATCTGCACGTAATCGGAATCGACCGTGGCGAACGTAATCTGATTTACGTATCAGTT ATCGACACATGTGGTAACATCGTGGAGCAGAAATCTTTTAACATTGTTAACGGCTAT GATTATCAGATTAAGCTTAAACAGCAGGAGGGGGCACGCCAAATCGCTCGTAAAGA ATGGAAGGAGATTGGAAAGATTAAAGAGATTAAAGAGGGGTACCTTTCGCTGGTTA TTCACGAAATTTCCAAGATGGTGATTAAGTACAATGCAATCATCGCGATGGAAGATC TTAGTTACGGATTCAAAAAGGGACGCTTCAAAGTTGAGCGTCAGGTCTACCAGAAA TTTGAAACGATGCTGATTAACAAATTGAATTACTTGGTATTCAAAGATATCTCAATT ACTGAAAATGGTGGCTTATTAAAGGGTTACCAGCTTACCTATATCCCGGATAAGCTG AAGAACGTGGGCCATCAATGCGGCTGCATCTTTTACGTCCCTGCCGCATATACCTCT AAAATTGACCCCACCACCGGATTCGTAAATATTTTTAAATTCAAGGACCTGACGGTG GACGCCAAGCGCGAATTCATCAAAAAATTCGACTCAATCCGCTATGATTCCGAAAA AAATCTTTTCTGCTTTACGTTCGATTATAATAACTTCATTACCCAAAACACGGTGATG TCAAAATCGTCCTGGAGCGTGTATACTTATGGAGTGCGTATCAAGCGCCGCTTTGTT AATGGGCGCTTCAGTAACGAAAGCGATACCATCGACATTACCAAAGACATGGAGAA GACGCTTGAAATGACGGATATCAATTGGCGTGACGGACACGATCTTCGTCAGGATAT CATCGACTACGAGATTGTGCAACATATCTTTGAGATTTTCCGTTTAACTGTTCAAATG CGTAACTCCTTGTCCGAATTGGAAGACCGTGATTACGACCGCTTGATTTCACCAGTG CTTAACGAGAATAACATCTTCTACGACTCCGCCAAAGCAGGCGATGCCCTGCCAAA GGACGCTGATGCAAATGGTGCATACTGTATCGCGTTGAAGGGCTTATACGAGATTAA GCAAATCACCGAAAATTGGAAAGAGGATGGAAAGTTCAGTCGCGATAAGCTGAAGA TCTCTAATAAAGATTGGTTTGACTTTATCCAGAACAAACGTTATTTA SEQ ID NO: 27 ATGAACAACGGTACCAATAATTTCCAAAATTTCATCGGAATCTCATCCTTGCAAAAA ACCTTGCGCAATGCTTTGATCCCCACCGAAACCACGCAGCAGTTCATCGTGAAAAAC GGCATTATCAAAGAGGATGAGTTGCGCGGGGAAAACCGTCAAATTCTTAAGGATAT CATGGACGATTACTACCGTGGGTTTATCAGTGAGACCCTGTCAAGCATTGACGACAT TGACTGGACCAGCTTATTTGAGAAGATGGAGATTCAATTAAAGAACGGGGACAATA AGGACACGCTTATCAAAGAGCAGACAGAATACCGTAAAGCGATTCATAAGAAATTT GCAAATGACGATCGCTTCAAGAACATGTTTTCAGCAAAATTAATCAGCGACATCCTT CCCGAATTTGTGATTCATAATAACAACTATTCGGCTAGCGAAAAAGAGGAGAAAAC TCAGGTTATTAAGCTTTTCTCGCGTTTTGCCACTTCGTTCAAAGACTATTTTAAGAAT CGCGCAAACTGCTTTTCGGCTGATGATATTTCCAGTTCTAGCTGCCATCGTATCGTTA ACGATAATGCTGAGATTTTCTTCTCTAATGCCCTGGTGTATCGTCGTATCGTTAAATC TTTGAGCAACGACGATATTAATAAGATTTCAGGCGACATGAAGGATTCTTTAAAGGA GATGTCTTTAGAAGAGATTTATTCCTATGAGAAATATGGCGAGTTTATCACCCAAGA AGGAATTTCGTTCTACAACGACATCTGTGGCAAAGTGAACAGCTTCATGAATTTATA CTGCCAAAAGAATAAGGAGAATAAAAATTTATATAAACTGCAGAAACTGCATAAGC AAATTCTTTGCATTGCAGACACCTCTTATGAAGTTCCTTATAAGTTTGAATCGGACG AGGAGGTATATCAGAGTGTGAACGGGTTCCTGGACAATATTTCATCCAAGCATATTG TTGAACGTTTACGCAAAATTGGAGACAATTACAATGGGTATAACCTTGACAAAATTT ACATCGTGTCGAAGTTTTACGAATCGGTAAGCCAGAAGACCTATCGTGACTGGGAA ACTATCAATACCGCCTTAGAAATTCATTACAACAATATTCTTCCTGGTAACGGCAAA AGCAAAGCCGATAAGGTAAAGAAGGCTGTCAAGAACGACCTGCAAAAGTCTATCAC AGAGATCAACGAGTTAGTCTCTAACTACAAATTATGTTCCGACGACAATATTAAAGC CGAAACCTACATCCATGAGATCTCACACATTCTTAACAATTTTGAGGCCCAGGAGCT GAAATATAACCCAGAAATTCACCTTGTAGAGAGCGAATTAAAAGCCTCCGAGCTGA AGAACGTTTTGGATGTAATCATGAACGCATTTCATTGGTGCAGCGTATTTATGACAG AGGAGTTGGTCGACAAGGACAATAACTTTTACGCCGAGCTTGAAGAAATCTACGAT GAAATTTACCCGGTAATTAGTTTATATAATTTAGTTCGCAACTACGTAACTCAGAAA CCCTACAGTACCAAGAAGATTAAATTGAACTTTGGGATCCCGACACTTGCTGACGGT TGGAGTAAATCAAAAGAATACTCCAATAATGCAATTATCCTGATGCGCGACAATCTT TACTACTTGGGGATCTTTAACGCAAAGAACAAACCAGATAAGAAAATCATCGAGGG CAACACCAGCGAGAATAAAGGCGATTACAAGAAAATGATCTATAATCTTTTGCCGG GACCGAACAAAATGATCCCAAAGGTTTTCCTGTCGTCGAAAACGGGAGTCGAGACA TATAAACCATCTGCGTACATCTTGGAAGGTTACAAACAGAATAAGCATATTAAGTCT AGTAAAGACTTCGACATCACCTTTTGTCATGACCTGATTGATTATTTCAAGAACTGT ATTGCTATCCATCCAGAATGGAAAAACTTCGGATTTGACTTCTCCGATACTAGCACC TACGAAGACATTTCGGGTTTTTATCGCGAAGTAGAGCTTCAAGGGTACAAAATTGAT TGGACATATATTAGCGAGAAAGACATTGATTTGCTTCAAGAGAAGGGACAGTTATA TTTATTCCAGATCTACAACAAAGACTTCTCGAAGAAATCCACCGGTAATGATAATCT TCACACTATGTACCTGAAGAATTTATTTTCAGAGGAAAATCTGAAGGACATTGTACT TAAACTTAATGGAGAAGCCGAAATCTTCTTCCGCAAGAGTTCCATTAAAAATCCGAT TATTCATAAAAAGGGAAGTATCCTTGTGAACCGCACGTATGAGGCCGAAGAGAAGG ATCAGTTTGGGAATATTCAAATTGTCCGCAAAAACATCCCCGAGAACATCTACCAGG AACTGTATAAATACTTTAATGATAAATCTGATAAAGAGTTATCAGACGAGGCTGCCA AACTGAAAAACGTAGTCGGTCATCATGAGGCAGCGACCAATATTGTAAAGGACTAC CGTTACACCTACGACAAGTATTTCCTTCACATGCCGATCACGATTAATTTTAAGGCT AACAAGACCGGCTTTATCAATGACCGCATCTTGCAGTACATCGCGAAAGAGAAAGA TTTACACGTCATCGGAATTGATCGTGGAGAGCGTAATCTTATCTACGTCAGCGTCAT CGACACCTGTGGAAACATTGTGGAACAAAAAAGTTTTAATATCGTAAACGGCTACG ACTATCAAATTAAACTTAAACAGCAAGAGGGAGCTCGCCAGATCGCTCGCAAAGAG TGGAAAGAGATTGGGAAAATTAAAGAAATTAAAGAGGGTTACCTGTCGCTGGTAAT TCACGAAATCTCGAAAATGGTCATCAAATATAATGCAATTATCGCTATGGAGGATCT GTCCTACGGGTTCAAGAAGGGACGTTTTAAAGTAGAGCGCCAGGTGTATCAAAAAT TCGAAACCATGTTGATCAATAAGCTTAACTATTTGGTCTTCAAAGATATTTCGATTAC GGAGAACGGAGGTTTGTTGAAAGGATATCAGCTGACGTATATCCCAGACAAGTTGA AAAACGTGGGGCATCAATGTGGATGTATTTTCTATGTGCCCGCGGCCTACACGAGTA AGATCGATCCTACCACTGGTTTCGTCAACATTTTCAAATTTAAAGATCTTACCGTGG ATGCGAAGCGCGAATTTATTAAGAAATTTGATAGCATTCGCTATGATTCCGAAAAGA ACCTGTTCTGTTTTACGTTCGACTATAACAATTTCATTACCCAAAACACGGTGATGA GCAAATCCTCTTGGTCAGTTTATACATACGGTGTACGTATCAAACGCCGTTTCGTTA ACGGACGCTTTTCCAATGAGTCTGATACAATCGATATCACGAAAGATATGGAAAAA ACATTAGAGATGACTGATATCAACTGGCGTGACGGGCACGACCTGCGTCAAGACAT TATTGACTACGAGATTGTGCAGCATATCTTCGAAATCTTTCGCTTAACTGTGCAAAT GCGTAACTCGTTATCCGAGTTAGAAGACCGTGACTACGATCGCCTGATTTCACCCGT CTTGAACGAAAATAACATCTTCTACGATTCCGCGAAGGCTGGGGACGCATTGCCCAA GGACGCAGACGCGAATGGAGCGTACTGTATTGCGCTTAAAGGATTATATGAAATCA AGCAGATCACCGAAAATTGGAAGGAGGACGGGAAGTTCTCACGCGACAAACTGAA GATTTCAAATAAGGACTGGTTCGATTTCATTCAGAATAAGCGTTACCTG SEQ ID NO: 28 TGAATAATGGTACGAACAACTTTCAGAACTTCATCGGCATCTCCAGCCTTCAAAAGA CTTTACGCAACGCATTGATTCCCACGGAGACTACGCAACAGTTTATCGTAAAAAATG GTATTATCAAAGAAGATGAATTACGCGGGGAGAATCGCCAGATTCTTAAGGACATT ATGGACGATTATTACCGTGGATTCATCAGTGAGACACTGAGCTCCATTGATGACATC GACTGGACGTCATTGTTTGAAAAGATGGAAATCCAGTTGAAAAATGGCGATAACAA AGATACATTGATTAAAGAGCAGACAGAGTACCGCAAAGCAATTCACAAGAAATTCG CCAATGATGATCGTTTTAAGAACATGTTTAGTGCCAAGCTTATTTCGGATATCTTACC CGAATTCGTGATTCACAACAACAATTATTCGGCAAGTGAGAAAGAGGAAAAGACCC AGGTTATCAAATTGTTTTCGCGCTTCGCCACTTCGTTCAAAGATTATTTCAAGAACCG TGCAAACTGTTTCTCCGCTGACGACATCAGTTCCAGCTCATGCCACCGTATTGTAAA TGACAATGCGGAGATCTTTTTCAGTAATGCCTTAGTATATCGTCGCATTGTAAAGAG CTTATCTAATGATGACATTAACAAGATCTCGGGTGATATGAAGGACTCACTTAAGGA GATGAGTCTGGAAGAGATCTACTCCTACGAAAAATACGGGGAATTCATCACCCAGG AGGGAATTTCATTCTACAACGATATCTGCGGCAAAGTTAACTCCTTTATGAATCTGT ACTGTCAAAAGAACAAGGAGAATAAAAACCTGTATAAATTGCAGAAACTTCATAAA CAAATTTTGTGTATCGCAGACACGAGTTATGAAGTACCTTATAAATTCGAATCCGAC GAAGAGGTATATCAGTCCGTAAATGGGTTCCTGGACAATATCAGTAGTAAGCACATT GTGGAACGCTTACGCAAAATTGGAGACAATTACAACGGGTATAACCTGGACAAAAT CTACATCGTATCCAAATTTTATGAAAGCGTGTCTCAAAAAACTTATCGTGATTGGGA AACAATCAACACGGCTCTTGAGATCCATTACAATAACATCTTGCCGGGTAACGGCAA ATCGAAGGCAGACAAAGTTAAAAAAGCAGTTAAGAACGACTTACAGAAAAGCATTA CGGAGATTAACGAGTTAGTAAGTAATTACAAATTATGCTCCGACGATAATATCAAA GCTGAAACCTACATCCATGAAATTAGCCACATTTTGAACAATTTCGAAGCGCAGGAG CTGAAATATAACCCTGAAATCCATCTGGTAGAGTCTGAGTTGAAGGCGTCAGAACTG AAAAACGTTCTTGACGTCATCATGAATGCCTTTCACTGGTGTAGTGTTTTTATGACTG AGGAGCTTGTAGATAAGGACAACAACTTCTATGCTGAACTTGAAGAGATCTACGAT GAAATCTACCCCGTAATCAGTCTGTATAATTTAGTTCGTAACTACGTCACGCAGAAA CCCTATTCGACTAAGAAAATTAAGCTGAACTTTGGGATCCCTACTTTGGCAGACGGG TGGAGCAAGAGTAAAGAATACAGTAATAATGCAATTATCTTGATGCGCGATAACTT ATATTACTTAGGTATTTTCAATGCTAAGAACAAACCTGATAAGAAGATTATCGAAGG AAATACGAGTGAGAATAAGGGAGACTACAAAAAGATGATTTACAACTTGCTGCCAG GGCCTAATAAGATGATTCCAAAAGTTTTTCTGTCGAGCAAGACAGGGGTTGAAACTT ATAAGCCATCCGCTTATATCCTTGAGGGGTACAAGCAGAATAAGCATATCAAGTCCT CCAAAGATTTTGATATTACATTTTGCCACGACTTAATTGATTACTTCAAGAACTGCAT CGCAATCCATCCCGAATGGAAGAATTTCGGCTTCGATTTCTCAGATACGTCCACGTA TGAGGATATCTCAGGCTTTTACCGCGAAGTTGAGCTGCAAGGTTATAAAATTGATTG GACATACATCTCCGAAAAAGACATTGATCTTTTACAGGAAAAGGGCCAATTATACTT ATTTCAAATCTATAACAAAGATTTTAGCAAGAAGTCCACAGGTAATGATAACCTGCA TACGATGTATTTGAAAAATCTTTTCAGTGAAGAGAATTTGAAGGATATCGTCCTGAA GCTGAACGGTGAGGCTGAGATCTTCTTCCGCAAATCGTCTATCAAAAACCCCATCAT TCACAAAAAGGGAAGTATCTTAGTAAACCGCACTTATGAAGCGGAGGAAAAGGATC AGTTCGGGAACATCCAGATCGTGCGCAAGAACATTCCAGAAAACATCTATCAGGAA CTTTACAAATATTTCAATGACAAGTCTGATAAAGAATTATCAGACGAGGCGGCGAA ACTTAAAAATGTTGTTGGACACCACGAAGCAGCGACGAATATTGTAAAGGATTATC GCTACACATACGATAAATACTTTTTGCACATGCCAATCACCATTAACTTTAAGGCGA ACAAGACAGGTTTCATTAACGACCGTATTCTGCAATATATCGCAAAGGAAAAAGAC CTGCACGTTATTGGGATCGATCGTGGCGAACGCAATTTGATCTACGTAAGCGTTATC GACACTTGCGGAAATATCGTTGAACAAAAAAGCTTTAATATCGTCAATGGATACGAT TACCAAATCAAGCTGAAACAACAAGAAGGGGCACGTCAGATCGCTCGTAAAGAATG GAAAGAGATTGGTAAGATCAAAGAGATTAAAGAAGGGTATCTTTCTTTAGTAATTC ACGAGATTTCGAAAATGGTTATTAAATACAATGCGATTATTGCTATGGAAGACTTAA GCTACGGCTTTAAGAAAGGTCGCTTCAAAGTGGAGCGCCAAGTGTATCAGAAGTTT GAAACGATGTTGATTAACAAATTAAATTACCTGGTCTTTAAGGACATCAGTATCACA GAAAATGGGGGGTTGCTTAAAGGGTACCAGCTTACATACATCCCTGATAAACTGAA AAATGTCGGTCATCAGTGCGGATGTATCTTCTATGTACCAGCAGCCTATACCAGTAA GATTGACCCTACTACTGGCTTTGTGAATATTTTTAAATTCAAGGATTTAACCGTGGAC GCCAAGCGTGAATTTATTAAAAAATTTGATTCGATTCGCTACGACAGTGAGAAAAAC CTTTTCTGCTTTACCTTTGACTACAACAATTTTATTACCCAGAACACCGTAATGTCAA AGAGTTCGTGGTCTGTATATACCTACGGTGTTCGCATCAAGCGCCGCTTCGTAAACG GGCGTTTCAGTAACGAATCTGACACCATCGACATCACTAAAGATATGGAGAAGACA TTGGAAATGACGGACATTAATTGGCGTGATGGCCATGACTTACGTCAGGACATTATT GATTACGAAATTGTGCAGCATATCTTCGAGATTTTCCGTTTGACAGTTCAGATGCGC AACTCACTGAGTGAGTTAGAAGATCGCGATTACGACCGTCTGATCTCACCGGTCCTT AATGAAAACAACATTTTCTACGACTCAGCAAAGGCGGGTGATGCCCTGCCAAAGGA TGCGGACGCTAATGGCGCCTACTGCATCGCCCTGAAAGGATTGTATGAAATTAAGCA GATTACAGAAAATTGGAAGGAAGATGGTAAATTTAGCCGTGATAAATTAAAAATCT CGAACAAGGATTGGTTCGATTTTATTCAGAACAAACGTTATTTG SEQ ID NO: 29 ATGAACAATGGAACAAATAATTTTCAAAATTTTATCGGCATCTCAAGTCTTCAAAAA ACCCTTCGCAATGCCCTGATTCCAACTGAAACAACCCAGCAATTTATCGTCAAGAAC GGCATCATTAAGGAAGACGAGTTACGCGGGGAGAACCGTCAAATCCTGAAAGATAT CATGGATGACTACTATCGTGGGTTCATTTCGGAAACCTTGTCTTCAATCGACGACAT TGACTGGACGAGTCTTTTCGAGAAAATGGAAATTCAGCTTAAAAATGGAGACAACA AGGATACTCTGATTAAGGAACAGACAGAATATCGCAAAGCTATCCACAAAAAGTTC GCTAATGATGATCGTTTCAAAAATATGTTTTCTGCTAAATTGATTTCCGATATCTTGC CTGAATTTGTAATCCACAACAACAATTATTCTGCTTCCGAGAAGGAAGAGAAGACCC AGGTCATTAAATTATTCAGCCGCTTTGCAACCAGCTTTAAAGACTACTTTAAGAATC GCGCTAACTGCTTTTCGGCGGATGACATCTCATCATCATCATGCCACCGCATTGTGA ACGACAATGCGGAGATCTTCTTTTCGAATGCGTTAGTTTATCGTCGCATTGTCAAAA GTCTTAGCAATGATGACATCAACAAGATCTCAGGAGACATGAAAGATTCCTTAAAG GAGATGTCTCTTGAGGAAATCTATTCGTATGAGAAATACGGCGAGTTCATTACCCAG GAAGGTATTAGTTTCTACAATGATATCTGCGGCAAAGTAAATTCTTTTATGAATCTG TATTGCCAAAAAAACAAAGAAAACAAGAATCTTTATAAGTTACAAAAGTTACATAA GCAAATTCTGTGCATCGCTGATACATCTTATGAGGTACCCTACAAATTTGAAAGTGA TGAGGAGGTCTATCAGAGTGTCAACGGCTTCTTAGACAACATCTCTTCCAAACATAT CGTGGAACGCCTGCGTAAAATCGGAGATAACTACAACGGATATAACTTAGATAAAA TCTACATCGTGTCCAAGTTTTATGAAAGTGTGAGCCAAAAAACATATCGTGACTGGG AAACCATTAACACCGCATTGGAAATTCACTATAACAACATTTTGCCAGGCAACGGG AAAAGTAAGGCGGACAAAGTTAAGAAAGCAGTTAAAAATGACCTGCAAAAAAGCA TCACTGAAATTAACGAATTGGTATCGAATTACAAATTATGTAGCGACGATAATATCA AAGCAGAAACTTACATTCACGAGATTAGTCACATTTTAAATAACTTCGAGGCCCAGG AATTGAAATACAATCCCGAAATTCATTTGGTTGAATCAGAACTGAAAGCATCAGAGT TGAAAAATGTGTTAGATGTCATTATGAATGCGTTTCATTGGTGCTCTGTGTTCATGAC CGAGGAACTGGTTGATAAAGATAACAACTTTTACGCTGAATTGGAGGAGATTTACG ATGAGATTTACCCGGTCATTTCGCTTTATAACTTAGTGCGCAATTATGTGACGCAGA AACCATATTCCACGAAGAAAATCAAACTTAATTTTGGCATCCCTACTCTGGCTGATG GTTGGTCGAAATCGAAAGAGTACAGCAACAACGCGATCATTCTTATGCGTGACAAT CTTTACTATTTGGGCATTTTTAATGCCAAGAATAAGCCAGATAAGAAAATCATTGAG GGGAATACTTCCGAGAATAAGGGGGATTACAAAAAGATGATCTATAACTTGCTGCC CGGCCCCAACAAAATGATTCCTAAGGTTTTCTTGTCAAGCAAGACGGGCGTCGAAAC ATATAAGCCGTCAGCTTATATTCTGGAAGGCTATAAACAGAATAAGCACATCAAGTC TTCCAAGGACTTTGACATCACTTTTTGCCACGATTTGATCGACTACTTTAAGAACTGT ATTGCGATTCATCCGGAATGGAAGAACTTCGGTTTCGACTTTTCCGATACCTCAACA TACGAGGATATCAGCGGCTTCTACCGTGAAGTCGAGCTTCAAGGCTACAAGATCGAT TGGACATATATTTCAGAGAAGGACATTGATTTGTTACAAGAGAAAGGTCAACTTTAC TTATTTCAGATCTATAACAAAGACTTTTCGAAGAAATCGACAGGAAACGATAACTTA CACACTATGTATTTAAAAAATCTGTTTTCGGAGGAAAACCTGAAAGATATTGTGCTG AAACTTAACGGCGAGGCAGAGATCTTTTTCCGTAAAAGCTCAATCAAGAATCCTATC ATCCATAAAAAAGGTAGTATTCTTGTCAACCGCACATATGAAGCGGAGGAGAAGGA CCAATTCGGAAACATCCAAATTGTCCGTAAGAATATTCCGGAGAACATTTACCAAGA GTTGTATAAATACTTTAACGATAAGTCAGATAAGGAACTTAGCGATGAGGCGGCGA AGCTTAAAAACGTAGTTGGGCATCATGAAGCTGCTACCAACATTGTAAAAGATTACC GTTACACCTATGACAAGTATTTCTTGCACATGCCCATTACGATCAATTTCAAAGCAA ATAAGACAGGCTTTATCAATGATCGCATCCTGCAGTACATTGCTAAAGAGAAGGATT TGCATGTTATCGGTATTGATCGCGGAGAGCGCAATTTGATCTACGTCTCCGTAATCG ACACTTGCGGTAACATTGTTGAGCAGAAGTCGTTCAACATCGTTAATGGTTATGATT ACCAAATCAAGCTGAAGCAGCAAGAGGGTGCCCGCCAGATCGCGCGTAAGGAATGG AAAGAAATCGGGAAAATTAAAGAGATCAAAGAAGGCTATTTGTCTCTGGTAATTCA CGAAATCAGCAAGATGGTGATCAAGTATAACGCGATCATTGCGATGGAGGATCTTT CTTATGGCTTCAAGAAAGGGCGCTTTAAAGTCGAACGCCAGGTCTACCAGAAATTTG AGACAATGCTTATCAACAAGCTTAACTATCTTGTATTTAAGGATATTTCCATCACTG AGAACGGAGGACTTTTAAAGGGGTACCAACTGACGTACATTCCTGATAAGCTGAAG AACGTTGGTCATCAATGCGGATGCATCTTCTATGTGCCAGCGGCTTACACCTCCAAA ATCGATCCCACTACAGGCTTTGTCAATATCTTCAAATTCAAGGATTTGACCGTTGAC GCGAAGCGCGAGTTTATCAAGAAGTTTGATAGCATTCGCTACGACAGCGAAAAAAA TTTATTTTGTTTTACTTTCGACTACAATAACTTTATTACTCAGAACACTGTCATGTCA AAGAGTTCGTGGAGTGTCTACACGTACGGAGTACGTATTAAGCGCCGTTTCGTCAAC GGACGCTTCTCAAACGAAAGCGACACGATCGACATCACCAAAGACATGGAAAAAAC TCTTGAGATGACGGATATCAATTGGCGCGACGGCCATGACCTGCGTCAGGATATCAT TGATTACGAGATCGTTCAGCACATCTTCGAAATCTTCCGCCTTACCGTCCAGATGCG CAACAGTTTAAGCGAGCTTGAAGACCGCGACTACGATCGTTTGATTAGCCCCGTTCT GAACGAGAATAATATTTTCTACGACAGCGCAAAGGCCGGTGATGCTTTGCCAAAGG ACGCAGACGCGAATGGAGCCTACTGCATCGCCCTGAAGGGCTTATATGAGATTAAG CAAATTACCGAAAATTGGAAGGAAGATGGTAAGTTCTCCCGTGATAAGCTTAAAAT TAGCAATAAGGATTGGTTCGACTTCATCCAGAACAAACGTTACCTG SEQ ID NO: 30 ATGAACAACGGAACAAACAATTTCCAAAACTTCATCGGTATCTCTTCGTTGCAGAAG ACTCTGCGTAATGCTTTGATCCCGACGGAGACAACCCAACAATTTATCGTCAAAAAC GGTATTATTAAGGAGGACGAGTTACGTGGAGAAAATCGTCAAATCCTTAAGGACAT CATGGACGATTATTATCGCGGGTTTATTTCTGAAACCCTGAGCAGTATCGATGATAT CGACTGGACCTCACTTTTTGAGAAAATGGAGATCCAGTTGAAGAACGGTGATAACA AAGACACTCTGATCAAAGAGCAAACTGAATACCGCAAGGCAATTCACAAAAAGTTC GCCAACGACGACCGTTTCAAGAATATGTTCTCAGCTAAGTTAATCAGCGACATTTTG CCAGAGTTCGTTATCCACAACAATAATTATAGTGCTTCAGAGAAGGAGGAAAAAAC CCAAGTGATTAAACTTTTTTCGCGCTTTGCAACCTCATTCAAGGACTACTTCAAGAAT CGCGCGAATTGCTTCAGTGCGGACGACATTTCTTCTTCAAGTTGCCATCGTATCGTTA ACGATAACGCGGAAATTTTCTTCTCTAATGCTTTGGTGTATCGCCGCATTGTAAAATC GCTTAGTAACGATGACATTAATAAGATCTCAGGTGATATGAAAGATTCATTGAAGG AAATGAGCTTGGAAGAGATTTACAGTTACGAAAAATATGGAGAATTTATTACTCAG GAAGGCATCTCATTCTATAACGATATCTGCGGGAAGGTAAATTCGTTTATGAACTTA TATTGCCAGAAAAATAAAGAGAATAAAAATTTGTATAAGCTTCAGAAGTTGCACAA ACAGATCCTGTGCATTGCAGACACCTCGTATGAGGTTCCGTATAAATTTGAGTCCGA TGAAGAAGTGTATCAGTCTGTGAATGGTTTCTTAGATAATATCTCTTCCAAGCATATT GTCGAACGCCTGCGCAAAATTGGTGATAACTATAACGGATACAATCTGGATAAAAT TTACATCGTTTCTAAATTTTACGAGTCAGTCTCGCAGAAGACCTACCGCGACTGGGA AACAATTAACACGGCATTGGAGATTCACTACAATAATATCTTGCCTGGTAACGGTAA GTCTAAGGCAGATAAGGTAAAAAAAGCTGTGAAAAACGACCTTCAGAAAAGCATCA CGGAGATTAATGAGCTGGTGAGTAATTACAAATTATGTTCAGACGATAATATTAAAG CTGAAACGTATATCCATGAAATCTCGCATATCTTGAACAACTTCGAGGCCCAAGAAC TTAAATATAACCCCGAAATCCATTTAGTCGAGTCTGAATTGAAAGCGTCGGAATTAA AAAACGTCTTAGACGTCATTATGAACGCGTTTCACTGGTGTTCAGTTTTCATGACCG AAGAGCTGGTCGACAAAGACAACAACTTCTATGCGGAATTGGAGGAAATCTATGAT GAAATCTACCCTGTTATTTCACTGTATAACCTTGTGCGCAACTATGTCACTCAGAAG CCGTATTCGACCAAAAAAATTAAATTGAATTTCGGTATCCCTACTCTTGCAGACGGA TGGAGTAAAAGCAAGGAATACAGTAATAACGCCATTATTCTTATGCGCGACAATTTA TACTACCTGGGCATCTTTAACGCAAAGAATAAGCCGGATAAGAAGATTATTGAGGG TAACACCAGTGAGAACAAGGGCGACTATAAGAAGATGATCTATAACTTATTGCCAG GTCCAAATAAAATGATCCCAAAAGTATTCTTATCATCAAAGACGGGAGTTGAAACCT ATAAGCCTAGTGCCTATATTCTTGAGGGATATAAACAGAACAAGCACATTAAGTCGT CTAAGGATTTTGACATTACGTTCTGCCATGACTTAATCGACTATTTTAAAAACTGTAT TGCGATTCACCCCGAATGGAAGAATTTTGGATTCGATTTTTCGGATACCTCGACCTA TGAAGATATTTCGGGATTTTATCGTGAAGTGGAGTTGCAAGGCTATAAAATCGATTG GACCTATATCTCAGAAAAAGACATTGATTTATTACAGGAAAAGGGACAACTGTACC TTTTCCAAATTTATAACAAGGACTTTTCTAAAAAGTCCACAGGAAATGATAACCTTC ACACCATGTACCTGAAGAACCTTTTCTCAGAGGAAAACCTGAAGGACATTGTCCTTA AGTTAAATGGAGAAGCGGAGATCTTTTTCCGTAAATCTAGTATCAAGAATCCGATTA TCCATAAAAAAGGTTCGATTTTGGTAAATCGCACCTATGAAGCGGAAGAGAAAGAT CAATTTGGTAACATCCAGATCGTGCGCAAGAATATCCCGGAGAACATTTACCAAGA GCTGTATAAGTACTTCAATGATAAGTCTGATAAGGAACTGTCAGATGAAGCTGCGA AATTGAAGAACGTGGTTGGGCATCATGAAGCCGCTACCAATATCGTCAAGGATTAC CGTTATACCTATGACAAATATTTCTTACACATGCCGATTACGATCAATTTTAAGGCA AACAAGACAGGATTCATCAACGACCGTATCTTGCAGTATATTGCCAAAGAGAAGGA TCTGCATGTGATCGGTATTGACCGCGGGGAGCGCAATTTAATCTATGTATCGGTGAT CGATACTTGTGGTAACATCGTAGAACAAAAGAGCTTTAACATCGTGAATGGTTACGA CTATCAGATCAAGCTGAAACAACAGGAAGGAGCCCGCCAGATCGCTCGCAAGGAAT GGAAAGAAATCGGGAAAATTAAGGAAATCAAGGAAGGCTACCTTTCATTGGTCATT CACGAAATTTCGAAAATGGTAATTAAGTACAACGCGATCATCGCCATGGAGGACCT TTCGTACGGATTTAAGAAGGGTCGTTTCAAAGTTGAGCGCCAGGTATACCAAAAATT CGAGACTATGCTTATCAACAAACTTAACTACTTGGTCTTTAAGGACATTTCTATTACC GAAAACGGCGGCTTACTTAAAGGCTATCAATTGACATATATTCCCGACAAACTGAA GAATGTTGGACATCAATGCGGGTGTATTTTCTATGTGCCGGCAGCTTACACTAGTAA GATCGACCCTACAACCGGGTTCGTAAACATTTTTAAATTCAAAGACTTAACAGTCGA TGCGAAGCGTGAATTTATTAAGAAGTTTGATAGTATCCGCTATGACAGTGAAAAGA ACTTGTTTTGCTTTACGTTCGACTACAATAACTTTATTACACAGAACACGGTCATGTC TAAATCATCATGGTCGGTTTACACATATGGGGTGCGCATCAAGCGTCGCTTTGTAAA TGGCCGTTTTAGTAATGAGAGCGACACAATCGACATCACAAAGGATATGGAGAAAA CTCTTGAGATGACAGACATCAATTGGCGTGACGGTCATGACTTACGCCAAGATATCA TCGACTACGAAATCGTACAGCATATTTTTGAGATTTTTCGTCTTACTGTGCAAATGCG TAATTCTTTATCCGAACTGGAAGATCGTGATTACGACCGCTTGATTAGTCCCGTCTTA AATGAGAACAATATTTTCTATGATTCTGCGAAAGCCGGAGATGCACTGCCCAAAGA CGCTGATGCCAATGGCGCGTATTGCATTGCATTAAAAGGATTATATGAGATTAAACA GATTACCGAAAATTGGAAAGAGGACGGTAAATTCTCACGCGATAAATTGAAGATTT CTAACAAGGACTGGTTCGACTTTATCCAAAATAAACGTTATCTT SEQ ID NO: 31 ATGAATAACGGTACCAACAACTTTCAGAATTTCATTGGCATTAGCTCGCTTCAAAAA ACTTTACGCAATGCTCTTATTCCGACTGAGACGACACAACAGTTTATCGTTAAGAAT GGCATCATCAAAGAAGATGAATTACGCGGAGAAAACCGCCAGATCCTGAAAGACAT TATGGACGATTATTACCGTGGGTTCATCTCCGAGACGTTGTCATCGATCGATGACAT CGACTGGACGTCACTTTTTGAAAAAATGGAGATCCAGTTAAAGAACGGTGACAATA AGGATACATTGATCAAAGAACAGACCGAGTACCGTAAAGCGATTCATAAAAAGTTT GCGAACGATGATCGCTTCAAGAATATGTTTTCTGCGAAATTAATTTCCGACATTTTA CCTGAATTTGTTATTCATAATAACAACTACTCGGCGTCTGAGAAAGAGGAGAAAACC CAAGTGATTAAACTTTTTTCACGTTTCGCAACGTCGTTCAAAGACTATTTTAAAAATC GTGCTAATTGCTTTAGCGCGGATGACATCAGCTCTAGTTCATGTCATCGCATTGTCA ACGATAATGCTGAGATCTTTTTCAGTAATGCGTTAGTGTACCGTCGTATTGTGAAGT CCTTATCTAATGATGATATCAATAAGATCAGCGGGGATATGAAGGACTCACTTAAGG AGATGAGCTTGGAGGAAATCTATTCCTATGAGAAGTATGGTGAGTTTATTACGCAAG AAGGAATTAGCTTTTACAACGATATCTGTGGAAAGGTGAATTCGTTTATGAATTTGT ATTGCCAGAAAAATAAGGAGAACAAGAACCTTTATAAATTGCAAAAGTTACACAAG CAAATCCTGTGCATTGCAGATACTTCCTACGAGGTGCCTTACAAGTTTGAATCCGAC GAAGAGGTCTACCAATCTGTAAACGGTTTCTTAGATAATATTAGTTCCAAGCATATT GTGGAGCGCCTTCGTAAAATTGGCGATAATTACAACGGTTACAATTTAGACAAAATT TACATTGTCAGTAAATTCTACGAGTCCGTATCTCAAAAGACGTATCGTGATTGGGAG ACTATCAATACGGCCCTGGAGATCCACTACAACAATATCTTGCCCGGTAATGGTAAG TCGAAGGCCGATAAAGTTAAGAAAGCGGTGAAAAATGACTTACAGAAGTCAATCAC CGAAATTAACGAATTGGTGTCCAATTATAAATTGTGTTCAGATGATAATATCAAAGC CGAGACCTACATTCATGAGATTTCCCATATCTTAAATAATTTCGAGGCGCAAGAGCT TAAGTATAACCCAGAAATCCACCTGGTAGAATCTGAGTTGAAGGCGTCAGAGTTAA AAAATGTTTTAGATGTCATTATGAACGCGTTTCACTGGTGCTCCGTATTTATGACGG AGGAATTAGTAGATAAAGACAACAATTTCTATGCCGAACTTGAGGAAATCTATGAT GAGATCTATCCCGTCATTAGCCTGTATAACTTGGTCCGCAACTATGTTACCCAAAAA CCGTACAGTACCAAGAAGATTAAGCTGAATTTCGGCATTCCTACACTGGCTGATGGT TGGAGTAAATCGAAGGAATATTCGAATAACGCGATTATCTTGATGCGCGACAACTTA TACTATTTGGGGATCTTTAACGCCAAAAACAAACCGGATAAGAAGATTATTGAGGG AAACACATCAGAGAACAAAGGCGACTACAAAAAAATGATTTACAACTTGTTACCGG GGCCTAACAAAATGATCCCGAAGGTGTTCTTATCCAGTAAAACAGGCGTTGAGACCT ACAAACCTTCCGCATACATCCTGGAAGGGTATAAGCAGAACAAGCACATTAAGTCC AGCAAGGATTTCGATATTACCTTCTGTCATGATTTAATTGACTATTTCAAGAACTGTA TTGCAATCCACCCCGAGTGGAAGAACTTCGGATTCGACTTCTCAGATACGAGCACAT ATGAGGACATCTCGGGGTTCTATCGTGAAGTAGAACTGCAGGGATATAAAATTGATT GGACATATATTTCCGAAAAAGACATCGACCTTTTACAAGAGAAGGGTCAACTTTACT TGTTCCAAATTTACAATAAAGACTTCTCAAAAAAAAGCACGGGTAACGATAATTTAC ACACTATGTATTTAAAGAACCTTTTCTCGGAAGAGAATTTAAAGGATATCGTATTGA AGTTGAATGGAGAAGCGGAGATCTTCTTCCGTAAGTCCAGTATTAAAAACCCTATTA TTCACAAGAAGGGATCGATTTTAGTTAACCGCACATACGAGGCCGAAGAGAAGGAC CAATTTGGGAACATTCAAATTGTCCGCAAAAACATCCCTGAGAACATTTATCAAGAG CTTTATAAGTACTTTAACGATAAGTCCGATAAGGAATTGTCAGATGAGGCGGCAAA GTTGAAGAATGTCGTGGGGCATCATGAAGCTGCCACCAACATTGTGAAGGACTACC GCTACACTTACGACAAATACTTCCTGCACATGCCCATTACGATCAATTTTAAGGCCA ATAAGACAGGCTTTATTAACGACCGTATTCTTCAATATATCGCTAAGGAGAAGGACC TTCATGTGATTGGGATCGACCGCGGAGAACGTAATTTAATTTATGTGTCCGTCATCG ATACGTGTGGAAATATCGTGGAACAGAAATCATTCAATATCGTGAATGGCTATGATT ACCAGATCAAATTAAAACAGCAGGAGGGCGCTCGCCAAATTGCGCGTAAGGAATGG AAAGAGATCGGAAAAATCAAAGAAATCAAAGAAGGATATTTGTCATTGGTGATCCA TGAGATTTCAAAAATGGTAATTAAATATAATGCAATTATCGCAATGGAAGACCTGTC CTATGGTTTTAAGAAGGGTCGTTTCAAGGTAGAACGCCAAGTGTATCAAAAGTTCGA GACGATGCTGATCAATAAGCTGAATTATCTTGTGTTTAAGGACATTAGCATCACGGA AAATGGAGGGCTGTTGAAAGGCTATCAACTGACGTATATCCCTGACAAGCTGAAAA ATGTTGGCCATCAGTGCGGGTGCATTTTCTACGTCCCCGCGGCGTATACAAGCAAGA TCGATCCTACTACGGGATTCGTAAATATTTTTAAATTCAAAGACTTAACCGTGGACG CCAAGCGCGAATTCATTAAGAAGTTTGATAGCATTCGCTACGATTCAGAAAAAAATC TTTTCTGTTTTACGTTCGATTACAACAATTTTATCACCCAGAACACAGTGATGAGCAA GTCATCCTGGTCTGTCTATACCTACGGTGTCCGTATCAAACGCCGCTTCGTCAACGG ACGCTTCTCTAATGAATCTGATACCATTGACATCACCAAGGACATGGAAAAGACACT TGAGATGACAGATATTAACTGGCGTGACGGACATGACCTGCGTCAGGACATCATCG ATTATGAGATTGTTCAGCATATCTTCGAGATCTTCCGCCTGACAGTACAAATGCGCA ATTCACTGTCAGAACTTGAAGACCGCGACTATGACCGCCTGATCTCTCCAGTATTAA ATGAGAACAATATCTTTTATGACAGTGCTAAGGCCGGCGATGCCCTTCCGAAAGATG CTGATGCTAACGGAGCTTATTGTATTGCATTAAAGGGTCTTTATGAGATCAAGCAAA TTACCGAGAATTGGAAGGAGGATGGCAAATTCTCGCGCGACAAACTGAAAATCAGT AACAAGGACTGGTTCGATTTTATTCAGAATAAACGTTACCTG SEQ ID NO: 32 ATGAATAACGGAACGAACAACTTCCAGAACTTCATCGGCATCAGTTCTTTACAAAAA ACCCTGCGTAACGCCCTTATTCCGACTGAGACAACACAACAGTTCATCGTTAAAAAC GGAATTATCAAAGAGGACGAGTTGCGCGGCGAGAATCGCCAAATTTTGAAAGATAT TATGGACGACTATTATCGTGGTTTTATTTCAGAAACACTGAGTTCGATTGACGATAT CGATTGGACGAGCCTGTTTGAGAAAATGGAAATCCAGTTGAAAAATGGCGATAATA AAGACACTTTAATCAAAGAACAAACCGAGTATCGTAAAGCGATCCATAAAAAGTTC GCTAATGACGATCGTTTTAAGAATATGTTCAGTGCGAAACTGATTTCAGACATTTTG CCCGAGTTCGTGATCCATAATAACAACTATTCCGCCTCGGAAAAGGAAGAAAAAAC CCAGGTGATTAAGCTGTTCAGTCGCTTCGCAACATCTTTCAAGGATTATTTCAAGAA TCGCGCGAATTGCTTCAGTGCGGACGATATTTCTAGTTCAAGCTGCCATCGTATCGTT AATGATAACGCGGAGATTTTTTTTAGCAATGCTCTGGTGTACCGCCGCATTGTTAAG TCACTGTCCAACGATGATATTAACAAGATCTCAGGAGACATGAAAGACTCGCTTAA AGAGATGAGTCTGGAAGAGATCTATTCTTATGAGAAGTATGGCGAGTTTATTACCCA AGAAGGAATCTCATTCTACAATGATATTTGTGGAAAGGTGAACAGCTTTATGAATCT TTACTGCCAAAAAAACAAGGAGAATAAGAATCTTTACAAACTTCAGAAGTTACATA AACAGATTTTGTGTATTGCGGATACGTCTTATGAAGTCCCCTACAAATTTGAATCGG ATGAAGAGGTATACCAAAGTGTGAACGGATTCTTGGACAATATTTCTTCTAAACATA TTGTTGAACGCTTACGTAAGATCGGGGATAACTACAATGGCTACAATCTTGACAAAA TCTACATTGTTAGCAAATTCTACGAGAGTGTCAGCCAAAAGACGTACCGCGATTGGG AAACAATTAATACTGCGCTTGAGATTCACTATAATAACATTTTACCAGGCAACGGCA AGTCCAAGGCGGATAAAGTTAAAAAAGCTGTTAAAAACGATTTGCAAAAATCTATC ACAGAAATTAACGAGTTAGTTAGTAACTACAAACTGTGCTCCGATGACAACATTAA GGCTGAGACGTATATCCATGAGATCTCTCACATCTTAAACAATTTTGAAGCTCAAGA ACTTAAGTACAATCCGGAAATCCACCTGGTGGAATCCGAGCTGAAGGCTAGCGAAC TGAAGAACGTATTGGACGTGATCATGAACGCGTTCCACTGGTGTTCTGTCTTTATGA CGGAAGAGCTTGTCGACAAAGATAATAACTTTTACGCGGAACTTGAGGAAATTTAC GATGAGATTTACCCAGTTATTTCATTGTATAACCTTGTCCGTAATTACGTGACCCAAA AGCCTTATAGTACGAAAAAAATCAAATTAAATTTTGGAATCCCAACACTGGCTGACG GTTGGAGCAAATCTAAGGAGTATTCTAATAACGCAATCATCTTAATGCGTGACAACC TGTATTATTTGGGTATCTTCAATGCCAAAAATAAGCCTGACAAAAAGATTATCGAAG GAAATACTTCGGAGAATAAGGGGGATTACAAAAAAATGATTTACAATTTGCTGCCC GGGCCGAACAAGATGATCCCCAAAGTGTTCTTATCCTCGAAGACTGGTGTAGAAAC ATACAAGCCAAGCGCATACATTCTGGAGGGTTACAAGCAAAACAAACACATCAAAT CTTCAAAAGACTTTGACATTACATTTTGCCATGATCTTATTGACTACTTCAAAAACTG CATTGCTATTCACCCCGAGTGGAAGAACTTTGGGTTTGACTTCAGCGACACGTCTAC GTATGAGGACATCTCCGGGTTCTACCGTGAAGTTGAGTTACAAGGGTATAAGATTGA CTGGACGTATATTTCAGAGAAAGATATCGATCTTTTGCAGGAAAAGGGCCAGTTATA TTTATTCCAGATTTACAACAAGGACTTTAGTAAGAAGTCAACAGGAAATGACAACTT GCATACGATGTATTTGAAAAATCTTTTTTCTGAGGAAAATCTTAAGGACATCGTACT GAAATTGAATGGCGAGGCTGAAATCTTCTTCCGTAAATCCTCCATTAAGAATCCCAT TATCCACAAAAAGGGGTCTATCCTGGTGAATCGTACCTACGAGGCAGAGGAGAAGG ATCAATTCGGAAATATTCAGATTGTTCGTAAGAACATCCCCGAGAACATTTATCAAG AATTGTATAAGTACTTTAATGACAAATCTGACAAAGAGTTATCCGACGAAGCTGCGA AACTGAAAAACGTTGTTGGTCACCACGAGGCCGCCACTAATATCGTAAAAGACTAC CGTTATACCTATGACAAGTACTTTTTGCACATGCCGATCACTATCAACTTCAAGGCG AATAAGACGGGCTTCATTAACGATCGTATCCTGCAATACATCGCCAAGGAGAAGGA CCTTCACGTCATTGGGATTGACCGTGGTGAGCGTAACCTGATTTATGTAAGCGTCAT TGATACCTGCGGTAATATCGTCGAACAGAAAAGTTTCAACATTGTAAATGGATATGA CTATCAGATCAAACTTAAGCAGCAGGAGGGTGCACGCCAGATTGCCCGCAAGGAAT GGAAGGAGATTGGGAAGATTAAGGAAATTAAAGAAGGTTACTTATCACTGGTTATT CACGAGATCAGTAAAATGGTAATCAAATATAACGCGATCATTGCCATGGAGGATCT GAGCTATGGCTTTAAAAAGGGCCGTTTCAAAGTCGAGCGCCAGGTATATCAAAAGT TTGAAACAATGCTGATTAACAAATTAAACTATCTGGTTTTCAAAGATATTTCGATCA CTGAAAATGGCGGGCTGTTGAAGGGATACCAACTTACATACATCCCTGACAAACTG AAAAATGTCGGTCACCAATGTGGATGTATCTTTTATGTACCAGCAGCGTATACGAGC AAAATCGATCCAACTACGGGTTTTGTGAACATCTTTAAGTTCAAGGATTTGACAGTA GATGCCAAACGCGAGTTCATTAAAAAATTTGATTCAATTCGCTACGATTCAGAGAAA AATCTTTTTTGTTTCACGTTCGATTACAATAATTTCATTACGCAGAACACAGTAATGT CAAAGTCAAGCTGGTCGGTCTACACGTATGGAGTCCGTATTAAACGTCGTTTTGTAA ACGGCCGTTTCTCAAATGAATCAGATACAATTGATATTACGAAGGATATGGAGAAG ACATTAGAGATGACTGACATTAACTGGCGCGACGGACATGATCTTCGTCAGGACATT ATTGATTATGAGATTGTACAGCATATCTTTGAGATCTTCCGCCTGACCGTTCAGATGC GCAATTCGTTGTCCGAGTTAGAAGACCGCGATTACGACCGTTTAATCAGTCCCGTCT TAAACGAAAATAACATCTTCTACGATTCAGCCAAGGCAGGCGATGCCTTGCCAAAG GATGCTGACGCAAATGGCGCATACTGTATTGCGTTGAAAGGCCTTTATGAAATCAAG CAAATTACCGAAAACTGGAAAGAAGACGGAAAATTCTCCCGTGATAAGTTGAAAAT CTCTAATAAGGATTGGTTCGATTTCATCCAAAATAAACGCTATTTG SEQ ID NO: 33 ATGAACAACGGAACTAATAATTTCCAAAATTTTATAGGCATCTCTTCTTTACAGAAG ACTCTTCGTAACGCCCTAATCCCGACTGAGACCACACAACAATTCATAGTGAAAAAT GGGATCATTAAAGAAGACGAGCTGCGTGGGGAGAACAGGCAGATCCTAAAAGACA TAATGGACGATTATTATAGAGGGTTCATCTCAGAGACATTATCTAGCATCGACGACA TTGACTGGACCTCCCTGTTTGAAAAAATGGAAATCCAGCTGAAGAATGGTGACAAT AAAGACACATTAATAAAAGAACAAACAGAGTACAGGAAAGCCATCCACAAGAAGT TCGCAAACGATGACAGATTCAAAAATATGTTCAGTGCGAAGCTAATATCCGACATCT TACCAGAGTTTGTAATACACAATAACAATTACAGCGCGAGCGAAAAGGAAGAGAAA ACGCAAGTAATTAAGCTTTTTAGTAGGTTCGCTACCTCTTTCAAAGATTACTTCAAA AATCGTGCTAACTGCTTCTCAGCCGACGACATATCTTCAAGTTCCTGTCACCGTATCG TGAATGATAACGCTGAGATATTCTTCTCAAACGCCCTTGTATACCGTAGGATCGTAA AGTCCTTATCTAACGATGATATAAACAAGATCAGTGGAGACATGAAAGACAGCCTT AAAGAGATGTCTCTAGAAGAAATTTACTCCTATGAAAAGTATGGGGAGTTTATAAC ACAGGAGGGGATCAGCTTCTACAACGACATCTGCGGAAAGGTGAACAGTTTCATGA ATCTTTACTGCCAGAAGAATAAAGAGAACAAAAATCTTTATAAGCTTCAAAAGTTGC ACAAACAAATACTGTGCATTGCCGATACATCATATGAGGTCCCCTATAAGTTCGAAT CTGATGAGGAAGTTTATCAATCTGTTAACGGCTTTCTAGACAATATCAGCTCAAAAC ACATCGTAGAAAGACTGAGGAAAATAGGTGATAATTATAATGGATACAACTTGGAT AAAATATATATAGTCTCTAAATTTTACGAGTCAGTATCCCAGAAAACGTATAGGGAT TGGGAGACCATCAACACGGCGTTAGAGATTCATTACAATAACATCTTACCGGGAAA CGGAAAAAGTAAGGCGGACAAAGTAAAGAAAGCCGTTAAAAATGACTTACAAAAG AGTATAACAGAAATAAACGAACTAGTAAGCAACTACAAGCTTTGTTCCGATGATAA TATCAAGGCCGAGACATATATCCATGAGATCTCCCACATTCTAAACAATTTCGAAGC GCAAGAACTTAAATATAATCCCGAAATCCACCTGGTGGAAAGTGAACTAAAGGCTA GTGAGTTAAAGAACGTTCTTGATGTTATCATGAACGCCTTCCATTGGTGCTCTGTTTT TATGACCGAGGAGTTGGTTGATAAAGATAATAATTTCTACGCTGAATTAGAGGAGAT ATACGACGAAATCTACCCAGTGATTTCACTATACAACTTGGTCAGGAACTATGTTAC ACAAAAGCCGTACAGCACTAAGAAAATTAAGCTAAATTTCGGTATCCCCACGTTAG CCGACGGGTGGAGCAAGTCCAAAGAATATTCCAACAATGCGATTATTTTAATGCGTG ACAATCTTTATTACCTTGGCATCTTCAATGCCAAAAACAAACCTGACAAAAAGATTA TAGAAGGTAATACGTCCGAGAACAAAGGCGATTACAAGAAGATGATTTATAACCTA CTGCCCGGACCAAACAAAATGATCCCCAAAGTTTTTCTTAGTTCTAAAACCGGCGTA GAGACGTATAAACCTTCTGCCTATATCTTAGAGGGATATAAGCAGAACAAACATATC AAATCTTCCAAGGACTTTGATATTACATTCTGCCACGATTTAATTGACTACTTCAAAA ATTGCATAGCGATACATCCGGAGTGGAAGAACTTTGGCTTCGACTTCAGTGATACAT CCACCTATGAGGATATATCAGGCTTCTATCGTGAGGTCGAATTGCAAGGGTACAAAA TCGATTGGACGTATATATCCGAGAAAGACATAGACCTTCTTCAAGAAAAGGGGCAG TTATATTTATTCCAAATATACAACAAGGACTTCAGTAAGAAGTCAACAGGTAATGAC AACTTACACACCATGTACTTGAAAAATTTATTTTCTGAAGAAAACCTAAAGGACATT GTACTAAAACTGAACGGGGAGGCAGAAATTTTTTTTAGAAAGAGCAGCATAAAAAA CCCAATAATTCATAAGAAAGGAAGCATTTTAGTTAATAGGACGTACGAGGCAGAGG AAAAGGACCAGTTTGGCAATATCCAGATCGTAAGGAAAAATATTCCTGAAAACATA TATCAGGAACTATATAAATACTTTAACGACAAATCCGACAAAGAATTATCCGACGA GGCTGCAAAGCTGAAGAACGTCGTAGGGCACCATGAGGCAGCGACTAATATTGTGA AAGACTATAGGTATACATACGACAAATACTTTCTGCACATGCCCATCACGATTAACT TCAAGGCGAACAAGACGGGATTCATTAACGACCGTATATTACAATATATTGCTAAG GAGAAAGATCTGCATGTAATAGGTATCGACAGAGGCGAACGTAATTTAATCTACGT GTCCGTCATCGACACGTGCGGGAACATCGTAGAGCAAAAGAGTTTTAATATAGTAA ATGGCTATGATTACCAAATTAAGCTAAAGCAGCAAGAAGGAGCAAGACAGATAGCT AGGAAAGAATGGAAGGAGATAGGAAAAATAAAGGAGATCAAGGAGGGGTATCTTA GCCTAGTAATTCATGAAATATCTAAGATGGTTATCAAATACAACGCTATCATAGCGA TGGAAGACTTATCTTATGGTTTCAAGAAAGGAAGGTTCAAAGTAGAGCGTCAAGTTT ATCAAAAGTTCGAAACGATGTTGATTAATAAACTAAACTATTTGGTATTTAAAGATA TATCTATCACCGAGAATGGTGGTCTACTAAAGGGTTACCAGCTTACATACATACCGG ACAAACTTAAAAACGTCGGACATCAGTGTGGATGCATTTTCTACGTTCCAGCTGCAT ATACCAGCAAGATCGACCCAACGACTGGGTTCGTAAATATTTTTAAATTCAAGGATT TGACTGTCGACGCCAAAAGAGAGTTCATAAAAAAGTTCGATTCAATTAGGTACGAC AGCGAAAAGAATTTGTTCTGCTTTACTTTTGACTATAACAATTTCATTACTCAGAACA CTGTAATGTCTAAGTCCTCTTGGTCAGTCTATACTTATGGCGTTCGTATCAAACGTAG ATTTGTTAACGGTAGATTCTCAAATGAAAGTGATACAATAGATATCACGAAAGATAT GGAGAAAACATTAGAAATGACAGACATAAACTGGAGAGACGGACATGACTTGAGA CAGGACATTATTGACTACGAGATCGTGCAGCACATCTTTGAGATCTTTCGTTTGACC GTACAAATGCGTAACAGTTTATCTGAGCTTGAGGACAGGGACTACGATAGATTGAT ATCACCTGTATTAAATGAGAATAACATCTTCTATGATTCCGCAAAAGCAGGCGACGC TCTACCCAAAGACGCTGATGCGAACGGTGCTTATTGCATAGCTTTAAAGGGTTTGTA TGAGATCAAACAGATAACAGAAAATTGGAAGGAAGATGGTAAGTTCTCCCGTGACA AGCTTAAAATATCAAATAAGGACTGGTTCGATTTTATACAGAATAAGCGTTATTA SEQ ID NO: 34 ATGAACAATGGAACTAATAACTTCCAGAATTTCATTGGTATCTCCTCTTTACAAAAA ACTCTAAGAAACGCCCTAATTCCGACTGAAACTACACAGCAATTCATCGTCAAAAAC GGGATCATTAAGGAGGATGAGTTGAGGGGTGAAAATCGTCAAATTCTTAAAGACAT CATGGACGACTACTACAGGGGGTTCATCAGCGAGACGTTATCTAGTATAGACGATAT AGACTGGACTTCACTGTTCGAGAAGATGGAAATCCAATTAAAAAATGGGGACAATA AAGATACACTTATAAAGGAACAGACAGAGTATAGAAAGGCAATACACAAAAAGTTT GCCAACGACGATCGTTTCAAGAACATGTTTAGTGCTAAATTGATTTCAGATATTCTG CCGGAATTTGTTATTCACAACAATAATTATAGCGCCAGTGAGAAAGAAGAAAAAAC GCAGGTTATCAAACTGTTCAGTCGTTTCGCTACATCTTTTAAGGATTACTTTAAAAAC CGTGCAAATTGTTTTTCAGCCGACGATATTAGTAGCAGCTCTTGTCACCGTATTGTTA ATGATAATGCGGAGATTTTCTTTTCAAACGCATTGGTCTACAGGAGGATAGTCAAGT CCCTTTCAAATGACGACATTAATAAGATCTCAGGTGACATGAAAGATTCCTTAAAGG AAATGTCCCTGGAAGAGATCTATTCCTATGAAAAGTACGGTGAGTTCATTACTCAAG AGGGTATAAGCTTTTACAATGACATATGTGGTAAGGTTAATAGCTTTATGAACCTGT ATTGCCAGAAGAACAAAGAAAATAAGAATCTGTATAAGTTGCAAAAGCTACACAAA CAAATTTTGTGCATTGCCGATACATCATACGAGGTGCCATACAAATTCGAGAGCGAT GAGGAGGTTTATCAGAGCGTGAATGGATTCCTGGACAATATTAGTAGTAAGCATATC GTGGAAAGGCTTAGAAAGATAGGTGACAATTACAATGGCTACAATCTGGATAAAAT CTACATCGTCTCAAAATTCTATGAAAGTGTATCCCAGAAGACGTACCGTGATTGGGA AACTATCAACACCGCTCTGGAGATACATTACAACAATATACTTCCCGGAAACGGCA AGTCAAAAGCCGACAAAGTCAAAAAAGCGGTCAAGAACGATTTACAAAAGTCTATC ACTGAAATTAATGAATTAGTTAGTAATTACAAACTGTGTAGTGATGATAATATTAAG GCAGAGACTTACATACACGAAATTTCACACATTTTAAACAACTTCGAGGCACAGGA ACTTAAATATAATCCTGAAATTCACCTGGTTGAAAGTGAATTGAAAGCCAGCGAGCT AAAGAACGTTTTGGACGTAATCATGAACGCATTCCACTGGTGCTCTGTCTTTATGAC AGAGGAACTAGTGGATAAGGACAATAATTTTTATGCGGAGCTGGAGGAAATATACG ATGAGATATATCCCGTAATATCATTATATAATCTGGTAAGAAACTATGTGACTCAAA AGCCGTATAGCACCAAGAAAATTAAACTTAATTTCGGCATACCCACTTTAGCGGACG GCTGGTCAAAATCCAAAGAGTATAGTAATAATGCCATCATCCTGATGCGTGACAACC TGTACTATTTAGGTATATTTAACGCCAAAAATAAACCCGACAAAAAGATTATAGAG GGCAACACCTCAGAGAACAAAGGTGATTATAAGAAGATGATTTACAACCTTTTACC CGGTCCTAATAAGATGATTCCCAAAGTCTTTCTATCTAGCAAAACTGGTGTTGAAAC ATACAAACCCTCAGCTTATATTTTAGAAGGGTATAAGCAGAATAAGCATATTAAAA GCTCCAAAGATTTCGATATTACCTTTTGCCATGACTTGATAGACTATTTCAAAAATTG TATTGCCATTCACCCTGAATGGAAAAACTTCGGATTTGACTTCTCTGACACATCCAC CTACGAAGACATTTCAGGTTTTTACAGGGAAGTCGAGCTACAGGGTTATAAAATTGA TTGGACATACATCAGCGAGAAAGATATTGACCTACTTCAAGAAAAAGGGCAGCTAT ACCTGTTCCAGATATACAATAAAGACTTCAGTAAAAAAAGCACCGGGAACGATAAT CTTCACACAATGTACTTAAAAAATTTATTTAGTGAAGAGAATCTGAAGGATATAGTG CTGAAGTTAAACGGGGAGGCAGAGATATTTTTTAGAAAATCTAGTATTAAGAATCC GATCATCCACAAGAAGGGTTCTATCCTTGTTAATAGGACTTATGAGGCAGAAGAAA AAGACCAATTCGGCAACATACAAATTGTCCGTAAAAATATCCCTGAGAACATTTATC AGGAACTATACAAGTACTTCAATGATAAAAGCGACAAGGAGCTGAGCGACGAGGCT GCTAAGTTAAAGAATGTGGTGGGCCACCATGAGGCAGCAACGAATATTGTGAAGGA CTATCGTTATACCTACGATAAATACTTTCTTCATATGCCGATCACCATTAATTTCAAG GCAAACAAAACTGGCTTCATTAACGATCGTATCTTACAATATATCGCAAAAGAGAA AGACCTTCACGTTATCGGGATCGATAGAGGCGAGCGTAACCTAATTTATGTTTCTGT GATAGACACCTGTGGGAACATAGTCGAACAGAAATCATTTAATATTGTTAACGGCTA CGATTATCAGATAAAGTTGAAGCAACAAGAGGGTGCACGTCAAATAGCAAGGAAAG AATGGAAAGAAATAGGCAAGATTAAAGAAATAAAAGAAGGTTATTTATCCCTTGTA ATACACGAAATTAGCAAAATGGTGATTAAATATAATGCGATCATTGCCATGGAGGA TCTTTCTTACGGCTTCAAAAAGGGGAGATTCAAAGTCGAGAGGCAGGTGTATCAGA AGTTTGAGACCATGCTAATCAATAAACTAAATTATCTAGTATTCAAAGACATAAGCA TCACCGAAAATGGCGGCTTGTTGAAGGGTTATCAATTGACCTACATCCCAGATAAAC TAAAAAACGTAGGGCATCAATGCGGATGTATATTTTACGTTCCAGCCGCATACACTT CCAAAATCGATCCAACTACGGGTTTTGTGAACATCTTCAAATTCAAAGACTTGACTG TCGATGCTAAGAGGGAGTTTATCAAGAAATTTGACTCCATTAGATACGACAGTGAG AAGAATCTGTTCTGTTTTACCTTTGATTATAACAACTTTATAACTCAAAACACAGTCA TGAGTAAGTCATCTTGGTCAGTGTATACGTATGGTGTGAGGATTAAAAGGAGGTTTG TTAACGGGAGATTTTCCAATGAAAGTGATACAATAGATATAACCAAGGACATGGAA AAGACTCTTGAAATGACCGACATTAACTGGAGAGATGGCCACGACTTACGTCAAGA TATAATCGATTACGAGATAGTGCAACATATCTTTGAGATATTTAGGCTTACTGTCCA AATGCGTAACTCATTAAGTGAGTTGGAGGACAGGGATTACGATAGGCTAATAAGTC CTGTTCTTAACGAAAACAATATATTCTACGATTCAGCAAAGGCGGGAGACGCCCTGC CCAAGGACGCGGATGCTAACGGCGCATACTGTATTGCCCTGAAAGGCTTGTACGAG ATAAAACAGATCACGGAGAACTGGAAAGAAGATGGAAAATTCAGTCGTGACAAGTT AAAAATTAGTAACAAAGACTGGTTCGACTTTATTCAGAACAAGAGATATCTG SEQ ID NO: 35 ATGAACAACGGAACCAATAACTTTCAAAACTTTATAGGCATCTCCAGTCTACAGAAG ACACTACGTAACGCTTTGATACCAACTGAGACCACGCAGCAGTTTATCGTCAAGAAC GGTATTATAAAGGAAGACGAGCTAAGGGGGGAAAACCGTCAGATCTTAAAGGACAT CATGGATGACTACTACAGAGGCTTCATAAGTGAGACTTTGTCTAGTATAGACGACAT CGACTGGACCAGTTTATTTGAGAAGATGGAAATTCAGTTAAAGAACGGGGACAATA AAGACACACTAATTAAAGAGCAGACCGAATACAGAAAAGCTATACACAAAAAGTTT GCCAACGATGATAGATTCAAAAATATGTTTTCAGCAAAATTGATTTCCGACATATTG CCAGAATTCGTAATCCATAATAACAATTATTCTGCAAGTGAGAAGGAAGAGAAGAC CCAAGTAATCAAGCTGTTTTCCCGTTTTGCTACGAGTTTCAAAGATTATTTCAAGAAT AGGGCTAATTGTTTCTCCGCGGACGACATAAGTAGCAGTTCCTGTCACAGGATTGTG AACGATAATGCTGAGATATTTTTTTCCAATGCCCTAGTGTATAGGAGAATAGTTAAA AGCTTAAGCAACGACGATATCAATAAAATTTCAGGGGACATGAAGGACAGCTTAAA GGAAATGAGTTTGGAGGAGATTTACAGTTATGAAAAATACGGAGAGTTTATAACTC AGGAAGGCATCTCTTTCTATAATGATATCTGTGGGAAGGTAAACTCCTTCATGAATT TATATTGCCAGAAGAATAAGGAAAACAAAAATCTTTACAAGCTTCAAAAGTTACAT AAGCAGATCTTATGTATTGCCGACACGAGTTATGAAGTGCCTTATAAATTCGAGAGT GATGAGGAAGTGTATCAGTCTGTTAACGGATTCCTAGATAATATAAGTTCCAAACAT ATAGTCGAGAGGCTGAGGAAGATTGGCGATAACTATAATGGATATAATCTTGACAA AATCTATATAGTCTCTAAATTTTATGAAAGCGTCAGCCAGAAGACATATAGAGATTG GGAAACTATAAACACAGCCCTTGAAATACATTACAATAACATCCTACCCGGCAATG GTAAGTCTAAGGCAGACAAAGTTAAAAAAGCAGTAAAGAATGACTTACAGAAGTCA ATCACGGAGATAAATGAGTTGGTCAGTAACTACAAATTATGCTCCGACGATAATATT AAGGCCGAAACATATATACACGAGATAAGTCATATATTAAACAATTTCGAAGCCCA GGAGTTAAAATATAACCCTGAAATTCATCTGGTCGAAAGTGAGTTAAAGGCCAGTG AGTTAAAGAATGTACTTGACGTAATTATGAATGCTTTTCATTGGTGCTCCGTGTTCAT GACCGAGGAGTTAGTAGATAAAGACAATAACTTTTACGCCGAACTTGAAGAGATAT ACGACGAGATTTATCCGGTAATCAGCTTGTACAACTTAGTTAGAAATTATGTAACAC AGAAGCCTTACTCTACTAAAAAAATAAAACTGAACTTTGGTATCCCAACTCTTGCAG ATGGTTGGAGTAAAAGCAAGGAATATAGCAACAATGCGATCATCTTGATGAGAGAC AACTTGTACTATTTGGGAATCTTCAACGCGAAAAATAAACCCGACAAAAAAATCAT CGAAGGGAATACCTCTGAGAATAAAGGTGACTATAAGAAAATGATTTACAATCTAC TTCCTGGTCCTAATAAAATGATCCCGAAAGTGTTTCTTAGTTCTAAGACTGGTGTCG AGACGTACAAACCTAGCGCGTACATCTTAGAAGGGTACAAGCAGAATAAACACATC AAATCAAGCAAAGACTTCGATATTACTTTTTGCCATGACTTGATAGACTACTTTAAA AACTGCATAGCAATCCACCCGGAGTGGAAAAACTTTGGCTTTGATTTCTCTGACACC TCTACATATGAGGACATATCTGGTTTTTACCGTGAGGTTGAATTGCAGGGATACAAA ATTGACTGGACTTACATATCTGAAAAAGATATCGATCTATTGCAGGAGAAAGGCCA GCTTTACCTTTTCCAGATCTATAATAAGGACTTCTCTAAGAAGTCTACAGGGAATGA TAATTTGCACACTATGTACTTAAAAAATCTGTTTTCCGAGGAAAACTTGAAAGACAT TGTTTTAAAGTTGAACGGAGAAGCTGAAATATTTTTCAGAAAGAGCTCCATAAAAA ACCCGATCATTCATAAGAAGGGATCTATCCTGGTTAACAGAACGTACGAAGCGGAA GAAAAAGACCAATTCGGAAACATTCAAATTGTTAGAAAGAATATCCCTGAGAACAT CTACCAGGAGTTATATAAGTATTTTAATGATAAGTCAGATAAGGAACTATCTGACGA AGCGGCGAAGCTTAAAAATGTTGTAGGACACCATGAGGCTGCTACAAATATAGTCA AGGACTACCGTTATACCTACGATAAGTACTTTCTACACATGCCCATTACCATCAATTT TAAAGCTAATAAAACGGGTTTTATCAACGATCGTATCCTACAATATATTGCGAAAGA GAAGGATTTGCATGTCATTGGCATTGATAGAGGTGAGAGGAACCTAATATACGTATC CGTGATTGATACGTGCGGGAACATAGTTGAACAGAAATCATTTAATATAGTTAATGG GTACGACTATCAGATTAAGCTAAAGCAACAAGAAGGCGCCAGGCAAATTGCCCGTA AAGAATGGAAAGAGATCGGGAAGATCAAGGAAATAAAAGAAGGATACCTTTCCCT GGTCATCCATGAAATTAGCAAAATGGTGATTAAGTACAATGCCATAATCGCGATGG AGGACTTAAGCTACGGGTTCAAAAAGGGGAGGTTTAAGGTGGAGAGGCAAGTGTAC CAGAAATTTGAGACCATGCTAATCAACAAACTGAACTACCTAGTTTTTAAGGACATT TCAATTACAGAGAATGGAGGACTTTTAAAGGGTTACCAACTAACGTATATACCAGAT AAGTTGAAAAATGTCGGTCACCAGTGTGGCTGCATCTTTTACGTTCCCGCCGCTTAT ACATCTAAAATTGATCCAACCACAGGCTTTGTAAATATCTTTAAATTCAAAGATTTA ACTGTGGATGCAAAAAGAGAGTTTATCAAGAAATTCGATAGCATTCGTTATGATAGC GAGAAGAACCTGTTCTGCTTTACTTTCGACTATAACAACTTTATAACTCAAAACACC GTGATGTCAAAAAGCTCATGGTCAGTCTACACCTATGGTGTAAGGATTAAAAGGCGT TTCGTGAATGGGAGATTCTCCAATGAAAGTGACACGATCGACATAACAAAGGACAT GGAGAAGACACTAGAGATGACTGATATTAATTGGAGAGACGGACACGATCTGCGTC AAGATATAATTGATTATGAGATAGTACAGCACATATTTGAGATCTTCCGTTTGACTG TCCAAATGCGTAATTCCCTTTCTGAGCTGGAAGATAGGGACTATGATAGATTAATAT CCCCTGTACTAAATGAGAACAACATTTTCTATGATAGTGCAAAAGCCGGGGATGCAT TGCCGAAAGACGCTGACGCTAATGGGGCGTACTGTATAGCTTTAAAGGGGCTTTACG AAATAAAGCAGATAACCGAAAACTGGAAGGAAGATGGCAAATTCTCAAGGGACAA ACTTAAGATCTCTAACAAGGATTGGTTCGATTTTATACAAAACAAACGTTATTTG SEQ ID NO: 36 ATGAATAATGGTACAAACAACTTTCAGAATTTCATTGGGATCTCTAGCTTACAGAAG ACCCTGAGGAATGCGTTGATTCCAACTGAAACAACCCAGCAATTCATCGTGAAAAA TGGGATAATCAAAGAGGATGAGTTAAGGGGTGAAAACCGTCAAATATTGAAGGATA TTATGGACGACTACTACCGTGGATTCATCTCAGAGACGTTGAGCAGCATTGACGACA TAGACTGGACTAGCCTTTTCGAGAAGATGGAAATTCAGTTAAAGAACGGAGATAAC AAAGATACACTAATCAAGGAACAGACAGAATACAGAAAAGCAATTCATAAGAAATT CGCTAATGACGATCGTTTTAAAAACATGTTCTCTGCAAAATTAATTAGCGACATTCT GCCGGAATTCGTTATACATAATAATAACTACAGTGCTTCTGAAAAGGAAGAGAAAA CTCAGGTAATAAAACTGTTCTCTCGTTTTGCCACATCCTTCAAAGACTACTTTAAAAA TAGAGCGAACTGCTTTAGCGCCGACGATATTAGTTCTTCCTCATGCCACAGGATTGT CAACGATAATGCAGAGATATTCTTTTCTAACGCACTAGTCTACAGAAGGATTGTAAA GTCTTTGTCAAATGATGACATAAACAAGATTAGTGGAGATATGAAAGACTCTCTAAA GGAAATGAGCCTTGAGGAGATATACTCTTATGAAAAGTACGGTGAGTTTATTACCCA AGAAGGCATTAGTTTCTATAATGACATTTGTGGAAAAGTTAACAGTTTTATGAATCT ATACTGTCAAAAAAATAAGGAGAATAAAAATCTTTATAAGTTGCAAAAACTGCATA AGCAGATATTATGTATAGCAGACACGAGCTATGAGGTACCGTACAAGTTCGAGAGC GATGAGGAAGTCTACCAATCTGTCAACGGATTTTTGGACAACATTTCTTCAAAACAT ATTGTGGAGAGGCTTAGGAAAATAGGCGACAATTATAATGGATATAACTTAGATAA GATATATATTGTTTCCAAATTCTACGAATCTGTAAGCCAGAAGACATACAGAGATTG GGAAACGATAAACACAGCCCTTGAAATTCACTATAACAACATACTACCTGGAAACG GCAAATCAAAGGCCGACAAAGTTAAGAAGGCCGTAAAGAATGATTTACAGAAGAG CATAACGGAGATCAATGAGCTGGTGTCTAACTATAAATTGTGTAGCGATGACAACAT AAAAGCCGAGACTTACATTCACGAAATTTCACACATACTTAACAACTTTGAAGCTCA GGAATTAAAGTATAATCCCGAAATACACCTTGTGGAGTCCGAACTAAAGGCTAGTG AGCTTAAGAACGTCCTAGACGTAATTATGAATGCCTTCCACTGGTGTAGTGTTTTTAT GACCGAGGAACTTGTTGACAAAGATAATAATTTTTATGCAGAACTAGAAGAGATAT ACGATGAAATATACCCGGTGATCAGTTTGTACAATCTTGTCAGGAACTATGTGACAC AAAAGCCCTATTCAACAAAGAAAATAAAACTTAATTTCGGAATTCCTACGTTAGCTG ATGGCTGGTCTAAATCCAAGGAATACAGCAACAACGCTATAATTCTGATGAGAGAT AACTTGTACTATCTAGGCATCTTCAATGCCAAAAATAAGCCTGATAAGAAGATTATA GAGGGCAACACTTCAGAGAACAAGGGCGACTACAAGAAAATGATCTATAACCTATT GCCTGGCCCAAACAAGATGATTCCGAAGGTCTTCCTATCATCCAAGACCGGCGTTGA GACATACAAGCCATCAGCGTATATTTTAGAGGGGTACAAACAAAACAAGCACATAA AGTCTAGTAAAGACTTCGATATAACATTTTGTCATGACTTAATTGACTACTTTAAGA ATTGCATCGCTATACACCCGGAATGGAAGAATTTCGGCTTCGACTTCTCTGATACAT CTACCTACGAGGACATTAGCGGGTTTTACCGTGAAGTCGAATTACAAGGGTATAAG ATAGATTGGACGTACATCTCTGAGAAAGACATAGACTTGCTTCAGGAAAAGGGCCA GTTGTATCTATTCCAAATATACAATAAGGATTTTTCCAAGAAATCTACGGGTAATGA CAATCTTCACACAATGTATCTTAAGAACCTTTTCTCAGAAGAGAACCTGAAGGACAT TGTCTTAAAACTAAATGGCGAAGCTGAGATTTTTTTCAGGAAGTCTTCAATTAAGAA CCCGATAATCCACAAGAAGGGGAGTATTCTTGTGAATAGAACTTACGAGGCCGAAG AAAAAGACCAATTTGGTAACATCCAGATAGTCAGAAAGAACATTCCAGAGAACATC TACCAAGAGCTATACAAATATTTCAACGACAAGTCCGATAAGGAACTGTCCGATGA GGCAGCCAAGTTGAAGAATGTCGTGGGTCATCATGAAGCTGCTACTAACATTGTCAA GGACTATCGTTATACTTACGACAAGTATTTCCTACACATGCCGATAACAATTAATTT CAAGGCTAACAAAACAGGCTTTATCAACGATCGTATCTTGCAGTACATAGCTAAGG AAAAGGATTTGCATGTGATTGGCATTGATAGAGGGGAGCGTAACTTGATATATGTGT CTGTCATAGACACGTGTGGCAACATCGTCGAACAGAAATCATTCAACATAGTAAAC GGCTACGATTACCAAATTAAGCTGAAACAGCAAGAGGGTGCACGTCAAATTGCGCG TAAAGAGTGGAAAGAAATTGGTAAAATCAAGGAAATTAAAGAAGGCTACTTGTCTC TTGTTATACATGAAATTTCCAAGATGGTTATAAAGTATAACGCGATAATTGCTATGG AAGACTTATCATACGGGTTTAAAAAGGGGAGGTTCAAGGTAGAGAGGCAGGTCTAT CAAAAGTTCGAGACGATGTTGATTAATAAACTAAACTATCTAGTGTTCAAAGATATC AGCATTACGGAGAACGGGGGGCTACTGAAAGGATATCAACTAACGTACATTCCCGA TAAGTTAAAGAACGTTGGTCATCAATGTGGTTGCATCTTCTACGTGCCTGCTGCCTAT ACGTCCAAAATAGATCCAACTACTGGATTTGTTAACATCTTTAAATTCAAAGATTTA ACCGTAGACGCCAAAAGGGAATTTATAAAAAAATTTGACAGCATCCGTTACGATAG CGAAAAGAATCTGTTCTGTTTTACTTTCGACTACAATAATTTCATCACGCAAAATAC GGTAATGTCTAAGTCAAGTTGGAGCGTCTACACGTATGGAGTCAGGATCAAGAGGC GTTTCGTAAATGGAAGATTCTCTAATGAGTCAGATACTATAGACATCACGAAAGATA TGGAGAAAACCTTGGAGATGACGGATATTAACTGGCGTGATGGACACGATTTAAGA CAGGACATTATTGACTATGAGATTGTGCAACACATCTTCGAAATATTCCGTCTAACA GTCCAAATGAGGAATAGCCTAAGTGAATTGGAGGACCGTGATTACGATAGGCTTAT AAGTCCTGTCCTTAACGAAAACAATATTTTCTATGATAGTGCTAAGGCGGGGGACGC ACTGCCTAAAGACGCAGATGCTAACGGGGCATACTGCATTGCGTTAAAGGGTCTGT ACGAAATCAAGCAGATTACGGAAAACTGGAAAGAGGATGGCAAGTTTAGCAGAGA TAAGTTGAAGATAAGTAACAAAGATTGGTTTGACTTTATTCAGAATAAAAGGTATTT A SEQ ID NO: 37 ATGAATAACGGCACTAATAATTTCCAGAATTTCATCGGCATTAGCAGCTTACAAAAG ACGTTGAGGAATGCCTTAATACCCACAGAAACTACTCAACAATTTATAGTGAAGAAT GGGATAATTAAGGAAGACGAGTTGAGAGGTGAAAATAGGCAAATCTTGAAAGACAT TATGGATGACTACTACAGGGGCTTCATTAGTGAAACGTTGTCTTCAATAGATGACAT TGATTGGACTTCTTTGTTTGAGAAGATGGAAATACAGTTAAAGAACGGCGACAATA AGGATACACTTATCAAAGAGCAAACAGAATATAGAAAAGCAATTCACAAAAAGTTT GCTAACGATGATAGGTTCAAGAACATGTTTAGCGCTAAACTAATATCAGACATCCTT CCCGAGTTCGTTATTCATAACAATAACTATAGTGCAAGTGAAAAAGAGGAGAAGAC ACAGGTGATTAAGCTGTTCTCCAGATTCGCGACTTCTTTCAAAGATTACTTCAAAAA CAGAGCCAACTGTTTTTCAGCTGACGATATCTCTAGTAGTAGTTGTCACCGTATAGT GAACGATAACGCTGAGATCTTCTTTAGCAATGCATTAGTGTATAGAAGGATAGTTAA GTCTCTAAGCAATGATGATATCAATAAAATTTCCGGAGACATGAAGGACTCCCTAAA GGAAATGTCCTTAGAAGAGATCTACTCATATGAGAAATACGGGGAATTTATTACGC AGGAAGGGATCTCCTTTTACAATGACATATGCGGGAAGGTCAACTCTTTCATGAACT TATACTGCCAAAAGAACAAGGAGAACAAGAATTTATATAAACTTCAGAAACTTCAC AAACAAATACTGTGCATAGCCGATACCTCATATGAGGTTCCTTACAAATTTGAATCA GATGAAGAGGTATACCAATCCGTTAACGGCTTTCTTGACAATATTAGCTCAAAGCAC ATCGTGGAGAGGTTGAGAAAGATTGGTGATAATTATAATGGCTACAATCTAGATAA GATATATATTGTTAGCAAGTTCTACGAGTCTGTGTCCCAAAAAACATATAGGGATTG GGAGACAATTAATACTGCTCTAGAAATCCATTACAACAACATCCTTCCTGGAAATGG CAAGAGTAAGGCCGACAAAGTCAAGAAAGCAGTGAAAAATGATCTGCAAAAATCA ATTACTGAGATAAACGAGCTAGTATCTAATTACAAGCTTTGTAGCGACGATAACATT AAGGCAGAAACGTACATACACGAGATTAGTCACATCTTAAATAATTTTGAAGCCCA AGAACTGAAATATAACCCTGAGATACACCTTGTTGAATCCGAGTTAAAGGCGTCTGA ACTAAAAAACGTGTTAGACGTTATTATGAATGCCTTCCACTGGTGTAGCGTCTTTAT GACTGAGGAGTTGGTTGATAAGGATAATAACTTTTACGCTGAATTGGAAGAAATTTA TGACGAAATCTATCCTGTTATTTCTCTATATAATTTGGTGAGAAATTACGTAACGCA AAAGCCCTATAGTACGAAAAAAATAAAACTAAATTTCGGGATCCCTACCCTAGCCG ACGGTTGGTCTAAATCCAAGGAGTACTCAAACAATGCAATAATATTGATGAGGGAC AACCTGTACTACCTAGGCATATTTAATGCCAAAAATAAGCCCGATAAAAAGATTATA GAAGGGAACACGTCAGAAAATAAAGGAGACTATAAGAAAATGATCTACAACCTTTT GCCCGGCCCCAATAAAATGATCCCGAAGGTCTTCCTAAGTAGCAAGACTGGCGTAG AGACCTACAAACCATCTGCATACATTTTGGAGGGGTACAAGCAAAACAAGCACATA AAGAGTAGTAAGGATTTTGACATTACATTCTGCCATGACTTAATTGACTACTTTAAA AATTGCATCGCAATTCACCCTGAATGGAAAAATTTTGGATTTGATTTCTCTGATACTT CAACATATGAGGATATTTCAGGGTTCTACAGGGAGGTCGAACTACAGGGTTACAAA ATAGACTGGACGTATATTTCTGAGAAAGATATAGATTTGCTTCAGGAAAAGGGTCA GCTATATCTGTTCCAGATATATAATAAGGACTTCTCCAAAAAGAGTACCGGAAATGA TAATCTGCACACAATGTACTTAAAAAACTTGTTCTCTGAGGAGAATCTAAAAGACAT CGTACTAAAACTTAACGGGGAGGCCGAAATTTTTTTTAGGAAGTCCAGCATCAAGA ACCCGATTATTCATAAAAAAGGTAGCATTTTGGTGAACCGTACTTATGAGGCGGAAG AAAAAGACCAATTCGGTAATATTCAAATCGTTAGAAAGAACATCCCTGAGAACATT TATCAGGAACTATACAAATACTTTAACGACAAATCAGATAAGGAGCTTTCTGATGAG GCAGCTAAATTGAAAAATGTAGTGGGACATCACGAAGCAGCCACTAACATAGTGAA GGACTACAGATACACATACGATAAGTACTTCCTGCACATGCCTATTACAATTAACTT TAAAGCAAATAAAACAGGGTTTATTAACGACAGAATCTTACAGTATATTGCCAAAG AAAAGGATCTGCATGTGATAGGAATAGACAGAGGAGAAAGAAACCTGATATACGTC TCCGTGATTGATACATGTGGGAACATAGTAGAACAGAAGTCCTTTAACATTGTTAAT GGGTACGATTATCAAATTAAATTAAAACAACAAGAAGGAGCACGTCAAATAGCTAG GAAAGAATGGAAAGAGATAGGAAAAATTAAGGAAATTAAGGAGGGTTACCTGTCC CTTGTAATTCATGAAATATCCAAAATGGTAATTAAATATAACGCGATCATCGCGATG GAAGATCTAAGCTACGGGTTCAAAAAAGGCAGGTTTAAGGTGGAGAGGCAAGTTTA CCAAAAGTTCGAGACAATGTTGATTAATAAGTTAAACTACTTAGTTTTCAAAGATAT CTCCATAACCGAGAATGGCGGGCTTTTAAAAGGGTACCAACTAACATATATCCCGG ATAAATTGAAGAACGTTGGACACCAGTGTGGCTGCATATTTTATGTACCCGCTGCGT ATACTTCTAAAATTGACCCGACCACCGGGTTTGTAAACATATTCAAGTTTAAGGACC TAACAGTTGACGCCAAACGTGAGTTCATCAAGAAGTTCGATAGTATAAGGTATGACT CTGAGAAGAACCTTTTCTGCTTCACGTTTGACTATAATAATTTCATCACCCAAAATAC AGTTATGTCAAAAAGCTCTTGGTCAGTATATACGTATGGCGTAAGGATTAAGCGTAG GTTCGTGAACGGTAGATTTTCCAACGAGTCAGATACTATTGATATTACCAAGGATAT GGAGAAGACATTAGAAATGACAGATATAAATTGGAGGGATGGGCACGATCTAAGGC AAGATATCATTGATTACGAAATTGTTCAGCACATATTCGAGATATTCCGTCTTACAG TACAAATGCGTAACAGCTTGTCTGAGTTGGAAGATCGTGACTATGACAGGTTGATAT CACCGGTCTTGAACGAGAACAATATATTCTACGACAGCGCTAAGGCGGGAGACGCT CTGCCTAAAGACGCAGATGCCAATGGGGCGTACTGCATTGCCTTAAAAGGCTTATAC GAGATTAAACAGATCACAGAGAACTGGAAAGAGGACGGCAAGTTTTCTAGAGATAA ATTGAAAATCTCAAACAAAGACTGGTTCGATTTCATCCAAAACAAAAGATACCTT SEQ ID NO: 38 ATGAACAATGGAACTAACAACTTCCAGAACTTTATCGGCATCTCTTCCCTCCAAAAG ACACTGAGAAATGCACTGATCCCAACCGAAACGACTCAACAATTTATTGTTAAGAA CGGCATCATAAAAGAAGACGAGCTTCGCGGCGAGAACCGCCAGATACTTAAGGATA TTATGGACGATTATTACCGAGGCTTTATCAGCGAAACTCTTAGCTCTATTGATGATAT CGACTGGACCTCCCTCTTCGAAAAAATGGAGATACAGCTCAAGAACGGCGATAATA AAGACACCTTGATAAAGGAACAGACTGAGTACAGGAAAGCGATCCACAAGAAATTC GCGAACGACGACAGGTTTAAAAACATGTTCTCTGCAAAATTGATATCCGACATCTTG CCGGAATTTGTGATACACAACAATAACTATAGCGCTTCAGAGAAAGAAGAGAAGAC CCAAGTAATCAAGTTGTTCAGCCGCTTCGCAACGTCTTTTAAAGATTACTTTAAGAA CCGGGCCAATTGTTTCTCCGCGGATGATATTAGCTCATCAAGTTGCCATCGAATTGT CAATGATAATGCGGAGATCTTCTTCAGCAATGCGCTGGTCTACAGACGAATCGTAAA AAGTCTTTCAAATGACGACATCAATAAGATTAGTGGAGATATGAAGGATTCCCTTAA GGAAATGAGTCTTGAAGAAATATACTCATACGAAAAGTACGGGGAATTTATTACCC AGGAGGGGATCTCCTTCTATAACGACATCTGTGGAAAAGTAAACTCATTCATGAACC TGTACTGTCAGAAAAACAAAGAAAACAAAAATCTGTATAAACTCCAAAAATTGCAC AAGCAAATATTGTGTATAGCGGACACATCATACGAGGTTCCATATAAGTTCGAAAGT GATGAAGAAGTCTACCAATCAGTGAATGGGTTTCTGGACAACATTAGTTCCAAGCAC ATAGTTGAACGACTGCGAAAGATTGGTGACAATTACAACGGCTATAATTTGGACAA GATTTATATAGTTAGCAAATTTTATGAATCCGTATCACAAAAGACTTATAGAGACTG GGAAACAATCAACACGGCACTTGAGATCCATTATAACAATATTCTTCCAGGGAACG GCAAAAGCAAGGCTGATAAGGTAAAAAAGGCCGTTAAGAATGATCTTCAAAAATCC ATAACGGAGATCAACGAACTTGTAAGTAACTACAAATTGTGCTCTGACGACAATAT AAAGGCTGAAACGTATATTCACGAGATTAGCCATATCCTGAATAACTTTGAGGCCCA AGAACTCAAGTATAACCCGGAAATACATTTGGTAGAAAGCGAGCTTAAAGCGAGTG AGCTGAAAAACGTCCTCGATGTGATCATGAATGCTTTCCACTGGTGTAGTGTCTTTA TGACTGAGGAGTTGGTTGATAAAGACAATAATTTCTACGCTGAACTGGAAGAAATTT ACGACGAAATCTATCCAGTGATCTCCCTCTATAACCTCGTTCGAAACTACGTGACGC AGAAACCTTATTCTACAAAGAAAATTAAGTTGAACTTCGGCATTCCTACACTTGCTG ACGGATGGTCCAAATCCAAAGAGTACTCAAACAACGCAATCATCCTCATGCGGGAT AACCTTTATTATTTGGGCATTTTCAACGCCAAAAACAAACCTGATAAAAAGATAATT GAAGGCAATACGAGTGAGAACAAGGGCGACTACAAAAAAATGATATATAACTTGTT GCCAGGCCCCAACAAGATGATTCCTAAAGTTTTTCTGTCTTCTAAGACTGGAGTTGA AACTTACAAACCCTCCGCCTACATTCTTGAAGGGTATAAACAGAATAAGCACATAA AGTCCTCAAAGGATTTCGACATTACGTTTTGCCATGACCTCATCGACTATTTCAAGA ACTGTATCGCCATACATCCGGAGTGGAAGAATTTTGGATTTGATTTCTCCGACACAT CTACCTATGAAGACATAAGCGGTTTCTACCGGGAGGTCGAGCTTCAGGGCTATAAG ATAGATTGGACATACATTAGTGAAAAAGATATCGATCTTCTGCAAGAAAAGGGACA ACTTTACCTTTTTCAGATTTATAATAAAGACTTTTCAAAAAAGTCCACAGGGAACGA TAATCTGCACACCATGTATCTCAAGAATCTGTTTAGTGAAGAAAACCTTAAAGACAT AGTTTTGAAGCTTAACGGAGAGGCTGAGATTTTTTTTAGAAAGTCCTCAATTAAAAA CCCTATAATACACAAGAAAGGCTCTATTCTTGTTAACAGGACATATGAAGCCGAGG AGAAAGATCAGTTTGGCAATATCCAGATTGTTCGCAAGAATATCCCGGAAAATATAT ATCAGGAGCTGTATAAATACTTTAACGACAAGAGCGACAAGGAGCTGAGTGACGAG GCCGCGAAGCTTAAGAATGTAGTAGGTCACCACGAAGCAGCCACCAATATCGTCAA AGACTATAGGTACACGTACGACAAGTACTTTTTGCACATGCCTATAACTATAAACTT CAAAGCTAATAAAACTGGGTTTATTAATGACAGGATTCTCCAATACATCGCTAAAGA GAAGGATCTGCATGTAATTGGCATAGACAGAGGTGAGAGAAACTTGATATATGTCA GCGTAATAGACACATGTGGCAATATCGTGGAACAGAAGTCTTTTAACATCGTCAATG GTTACGACTACCAAATTAAGTTGAAACAGCAGGAAGGCGCACGACAGATCGCACGA AAGGAATGGAAAGAGATAGGCAAAATAAAAGAAATAAAGGAGGGCTATCTCAGTC TCGTTATACACGAAATTTCAAAAATGGTTATTAAGTACAATGCAATCATAGCGATGG AGGATCTCAGTTATGGGTTCAAAAAGGGTCGGTTTAAAGTTGAGCGCCAAGTGTACC AAAAGTTCGAGACAATGCTGATTAACAAGCTGAACTACCTCGTCTTCAAAGATATAA GTATTACGGAGAACGGTGGCCTTCTTAAAGGCTATCAACTTACTTACATCCCGGACA AGCTCAAAAACGTAGGGCACCAATGCGGGTGTATTTTCTATGTGCCTGCGGCATATA CGTCAAAGATTGACCCAACCACAGGATTCGTAAACATATTCAAGTTTAAGGACCTCA CCGTTGATGCGAAAAGGGAGTTCATTAAAAAATTTGATTCTATTCGATATGATAGTG AGAAAAATCTCTTTTGTTTCACATTTGACTATAATAATTTTATTACTCAGAATACTGT CATGAGCAAGTCATCTTGGTCAGTGTACACATACGGGGTGCGGATCAAACGCAGGT TCGTCAATGGTCGCTTCTCAAACGAATCAGACACCATTGACATCACAAAGGACATGG AAAAAACCCTTGAGATGACCGACATTAATTGGCGCGATGGTCATGATCTGCGGCAA GACATCATAGACTACGAAATCGTCCAACACATCTTTGAGATCTTTCGCTTGACGGTC CAAATGCGGAACTCCCTGTCCGAGCTCGAGGATAGAGATTATGATCGGCTGATATCT CCCGTGCTTAATGAAAATAACATCTTCTACGACTCCGCCAAGGCGGGTGATGCCCTG CCGAAGGATGCGGATGCTAATGGCGCTTATTGCATTGCTCTTAAGGGGCTCTATGAG ATAAAGCAGATCACGGAAAACTGGAAAGAAGACGGTAAGTTTAGTAGAGACAAGC TGAAGATCTCAAATAAAGACTGGTTTGATTTCATACAG. AAC. AAG. CGG. TAC. CTG SEQ ID NO: 39 ATGAACAATGGCACTAACAATTTTCAGAATTTCATCGGCATTTCAAGTCTGCAAAAA ACTCTGAGGAATGCTTTGATCCCTACTGAAACCACTCAGCAATTTATAGTCAAGAAC GGTATAATTAAAGAAGATGAACTCAGGGGTGAAAATAGACAAATACTCAAGGACAT TATGGATGACTATTATAGAGGCTTCATCTCAGAGACTCTCTCATCAATAGATGATAT CGATTGGACTAGCCTTTTCGAGAAAATGGAGATTCAGTTGAAAAATGGTGATAACA AAGATACGTTGATAAAGGAACAGACCGAGTACAGGAAAGCCATTCATAAGAAATTT GCTAATGACGATAGATTTAAGAATATGTTTAGTGCAAAACTGATTAGTGACATTCTG CCGGAGTTCGTTATCCATAATAATAACTACTCTGCATCCGAAAAGGAGGAAAAGAC GCAAGTTATTAAACTGTTCAGCCGCTTCGCCACAAGCTTCAAGGACTACTTCAAAAA TAGAGCCAACTGCTTTTCTGCCGACGATATATCATCATCTTCATGCCATCGGATCGTT AACGATAACGCCGAGATATTCTTCAGCAACGCCCTTGTATATCGAAGAATAGTCAAA AGTCTGAGTAATGATGATATTAATAAAATTAGCGGTGATATGAAAGACTCCCTGAA GGAAATGTCACTGGAGGAAATTTATAGTTACGAAAAGTACGGCGAATTCATTACTC AAGAAGGCATATCCTTCTATAACGACATTTGCGGAAAGGTCAACTCATTCATGAACC TTTATTGCCAGAAGAATAAGGAGAATAAAAATCTTTACAAATTGCAAAAACTTCAC AAACAAATTCTTTGCATCGCGGATACGTCCTACGAAGTTCCTTACAAATTTGAATCC GATGAGGAAGTGTATCAGAGTGTCAATGGATTTTTGGATAATATCTCTTCAAAACAT ATTGTGGAGAGATTGCGCAAAATAGGTGATAACTACAATGGCTACAACCTGGACAA GATTTATATTGTTAGCAAGTTCTATGAAAGTGTCAGTCAAAAGACCTACAGAGATTG GGAGACAATCAACACGGCGCTCGAAATACACTACAATAACATCCTCCCCGGCAATG GGAAGAGTAAAGCCGATAAGGTTAAAAAAGCTGTTAAGAACGACCTCCAGAAATCC ATCACGGAAATAAACGAGCTGGTTTCCAACTATAAGCTGTGTAGCGATGATAATATT AAGGCTGAGACATATATACATGAGATCAGCCACATTCTCAACAATTTCGAGGCACA GGAACTCAAATACAATCCCGAGATTCACTTGGTGGAAAGTGAGTTGAAGGCGTCAG AGCTTAAGAATGTACTTGACGTAATAATGAATGCTTTTCATTGGTGCTCCGTGTTCAT GACTGAGGAACTCGTGGATAAGGATAATAACTTTTATGCGGAGTTGGAAGAGATAT ACGATGAAATATACCCGGTTATCTCACTGTATAATCTGGTCAGAAATTACGTGACCC AAAAGCCTTATAGTACAAAAAAAATAAAGTTGAACTTCGGTATTCCGACATTGGCA GATGGTTGGTCCAAAAGCAAAGAATACTCTAATAACGCCATTATATTGATGCGAGA CAATTTGTATTACCTTGGGATCTTTAACGCGAAAAACAAACCGGATAAGAAGATCAT CGAAGGTAATACATCTGAGAATAAGGGGGATTACAAGAAGATGATTTATAATCTGT TGCCGGGGCCAAACAAGATGATTCCGAAGGTCTTTCTGTCATCTAAGACAGGAGTA GAGACCTACAAACCTTCTGCGTACATTTTGGAAGGCTACAAACAGAACAAGCATAT AAAATCTAGCAAGGACTTTGATATCACGTTTTGTCATGATCTGATAGATTATTTCAA AAACTGCATCGCTATACATCCTGAGTGGAAGAATTTCGGCTTTGACTTTTCTGACAC CAGCACATACGAAGACATCTCAGGTTTCTACCGGGAAGTCGAGCTCCAGGGGTACA AGATTGACTGGACATATATAAGTGAAAAAGACATCGACCTCCTCCAAGAGAAGGGC CAACTTTACCTGTTCCAGATCTATAACAAAGACTTTTCTAAAAAGTCCACGGGTAAC GACAACTTGCACACTATGTATCTGAAAAACTTGTTCTCTGAAGAGAACCTCAAGGAC ATCGTCCTGAAGCTTAACGGGGAGGCGGAGATCTTCTTTAGAAAGTCCTCTATCAAA AATCCCATTATCCATAAAAAGGGCTCTATACTCGTTAATAGGACATATGAAGCGGAG GAAAAAGATCAATTTGGGAACATCCAGATCGTCCGGAAAAATATACCTGAGAATAT CTATCAAGAGCTGTACAAGTATTTTAATGATAAGTCAGACAAAGAGCTCAGTGATG AGGCGGCAAAGCTCAAGAACGTGGTGGGGCATCATGAAGCTGCGACGAACATTGTC AAAGATTATAGATACACTTACGATAAATACTTCCTCCACATGCCGATAACGATTAAC TTCAAAGCCAATAAGACGGGGTTTATAAATGATCGGATCCTTCAGTACATTGCGAAA GAGAAAGACCTCCATGTGATCGGAATTGACCGAGGAGAAAGGAATCTGATTTACGT GTCCGTGATTGATACTTGCGGGAATATAGTCGAGCAAAAGAGTTTCAACATAGTCAA CGGGTATGACTATCAGATAAAGCTCAAACAGCAGGAAGGTGCGAGGCAAATTGCGC GCAAAGAGTGGAAGGAGATAGGCAAGATTAAAGAAATCAAGGAAGGTTATCTCAG CTTGGTGATCCATGAAATATCTAAGATGGTTATAAAGTACAATGCCATAATAGCCAT GGAGGATCTTTCCTACGGGTTTAAGAAGGGCCGATTTAAAGTGGAGCGACAAGTTT ACCAGAAGTTCGAAACCATGTTGATTAACAAACTTAACTATTTGGTGTTCAAGGATA TAAGTATAACCGAAAACGGCGGTTTGCTTAAGGGTTATCAGCTCACGTATATTCCTG ATAAACTTAAAAACGTTGGACACCAGTGTGGATGTATCTTCTACGTGCCAGCCGCTT ACACTAGTAAGATAGATCCTACCACGGGGTTTGTGAATATTTTTAAGTTTAAAGACT TGACAGTCGACGCCAAAAGGGAATTTATAAAAAAGTTTGATTCTATCCGCTACGATA GTGAAAAAAATCTCTTTTGCTTTACTTTCGACTATAACAACTTCATTACGCAGAACA CTGTCATGAGTAAGTCCAGCTGGAGCGTCTACACATATGGCGTCCGAATTAAACGAC GATTTGTAAACGGGCGGTTTTCAAACGAATCTGACACGATAGACATTACCAAGGAT ATGGAGAAGACACTTGAGATGACCGACATAAACTGGCGGGACGGTCACGATCTTCG GCAGGACATAATTGATTACGAAATCGTCCAGCATATATTCGAAATATTTCGACTTAC AGTGCAAATGCGGAACAGTCTCTCTGAACTGGAAGATCGCGATTATGACCGGTTGAT TTCTCCGGTCCTCAATGAAAATAACATATTTTATGATAGTGCTAAGGCAGGTGATGC GTTGCCAAAGGATGCAGACGCTAATGGTGCCTATTGTATCGCGCTCAAGGGATTGTA CGAGATAAAGCAAATTACGGAGAACTGGAAGGAGGATGGTAAGTTTAGCCGAGAC AAGTTGAAGATTAGCAATAAAGACTGGTTTGATTTTATCCAAAACAAGAGGTACCTG SEQ ID NO: 40 ATGAATAACGGAACTAATAACTTTCAAAATTTCATAGGTATTTCAAGCTTGCAGAAG ACCCTGAGGAATGCCCTGATTCCAACCGAGACAACGCAGCAGTTCATAGTCAAAAA TGGCATTATTAAGGAAGATGAGCTGCGGGGGGAAAACCGACAGATACTCAAGGATA TTATGGACGACTATTACCGGGGATTTATCTCAGAAACGCTGAGCAGTATTGATGACA TCGATTGGACCAGTCTTTTCGAGAAAATGGAAATTCAACTTAAGAATGGTGACAATA AAGACACTCTCATAAAGGAGCAAACTGAATACCGAAAAGCCATACACAAAAAGTTT GCCAACGATGACCGCTTTAAAAACATGTTTTCAGCTAAGCTCATTAGCGACATTCTC CCCGAGTTTGTGATTCATAACAATAACTATAGCGCATCCGAGAAGGAGGAAAAAAC CCAAGTTATCAAATTGTTCAGTAGATTCGCTACGAGCTTTAAAGATTACTTTAAAAA CCGGGCTAACTGCTTCAGTGCAGACGATATCAGCTCCTCATCCTGTCATCGCATCGT CAATGATAATGCTGAGATCTTCTTTTCTAATGCACTGGTTTACCGCAGGATAGTTAA GTCTCTTAGTAACGACGACATCAACAAGATATCAGGAGATATGAAGGATTCCCTTAA AGAAATGAGTCTCGAGGAGATATATTCTTATGAAAAATACGGCGAATTTATTACCCA AGAGGGCATTAGTTTCTATAATGACATATGCGGAAAAGTTAATAGTTTTATGAATCT CTATTGTCAGAAGAATAAGGAGAATAAGAACCTCTACAAATTGCAGAAGTTGCACA AGCAAATTCTGTGTATCGCGGACACCTCTTACGAGGTCCCATATAAGTTCGAGAGTG ATGAAGAAGTATACCAGAGCGTTAATGGGTTCCTGGACAACATCTCAAGTAAACAC ATAGTCGAAAGGCTCCGAAAGATCGGTGATAACTATAACGGATATAATTTGGATAA AATTTATATAGTTAGCAAATTTTACGAGAGCGTCAGTCAGAAGACCTACCGGGACTG GGAGACCATAAACACAGCGCTGGAAATACATTATAACAACATACTGCCTGGGAACG GTAAGTCAAAGGCAGACAAGGTTAAAAAGGCTGTGAAGAATGACCTGCAAAAATCA ATTACAGAAATAAATGAGTTGGTAAGTAATTACAAACTTTGCAGCGATGATAATATA AAGGCAGAGACGTACATACATGAAATATCTCATATCCTCAACAATTTCGAAGCCCA AGAACTGAAGTACAACCCGGAAATTCATCTTGTAGAGTCTGAGTTGAAGGCCTCCG AATTGAAAAACGTTCTTGACGTAATTATGAATGCCTTCCACTGGTGCTCAGTATTCA TGACGGAAGAGCTCGTGGATAAAGACAACAATTTTTACGCTGAACTGGAAGAAATA TATGACGAGATTTACCCCGTAATTTCACTCTACAACTTGGTACGAAATTACGTTACC CAAAAGCCATACTCAACAAAAAAAATTAAACTGAACTTCGGGATACCCACCCTCGC AGATGGATGGTCAAAGTCCAAAGAGTACAGTAACAATGCAATTATCCTGATGCGAG ACAACCTTTATTACCTCGGGATTTTCAACGCTAAAAATAAACCTGATAAAAAAATAA TTGAGGGTAATACCTCTGAAAACAAGGGGGATTATAAAAAGATGATATACAATCTG CTGCCTGGCCCGAACAAAATGATTCCTAAAGTCTTCTTGTCTTCCAAGACTGGAGTC GAAACCTACAAGCCAAGTGCTTATATACTCGAAGGGTACAAACAAAATAAGCACAT AAAATCCAGCAAGGATTTTGATATTACATTCTGCCACGATTTGATTGATTATTTTAAG AACTGTATAGCCATCCACCCAGAATGGAAGAATTTTGGTTTTGATTTTAGCGATACC TCAACATATGAGGATATCTCTGGCTTTTACCGCGAGGTAGAACTGCAAGGTTATAAG ATCGATTGGACTTATATTTCTGAAAAGGACATAGATCTCCTGCAAGAGAAAGGGCA ACTTTATTTGTTTCAAATATACAACAAAGATTTTAGTAAGAAGAGTACTGGCAATGA TAACCTTCACACTATGTATCTGAAGAACCTTTTTTCTGAGGAGAACTTGAAGGACAT AGTCCTTAAACTCAATGGGGAAGCTGAAATATTCTTTCGCAAAAGCTCCATTAAAAA CCCGATCATTCATAAAAAGGGTTCCATCTTGGTAAACCGCACATACGAGGCGGAAG AAAAAGATCAGTTCGGAAATATCCAGATCGTAAGGAAGAATATCCCCGAAAATATA TACCAAGAGCTTTACAAATATTTTAACGATAAGTCAGACAAGGAACTGTCAGACGA AGCAGCCAAGTTGAAGAATGTCGTAGGGCACCACGAAGCAGCTACAAACATAGTTA AAGATTATCGGTACACCTACGATAAATATTTCCTGCATATGCCAATAACCATAAACT TCAAAGCCAACAAAACAGGGTTCATCAATGACCGAATACTTCAGTATATAGCCAAG GAAAAAGACCTGCATGTTATAGGAATAGATAGAGGTGAGCGCAACTTGATATATGT CAGCGTGATAGACACCTGCGGAAATATCGTCGAGCAAAAAAGTTTCAACATTGTTA ATGGCTACGATTACCAAATTAAATTGAAGCAGCAAGAGGGGGCTCGGCAAATCGCG CGAAAGGAATGGAAAGAAATCGGGAAGATTAAAGAAATTAAAGAGGGCTACCTGT CTCTTGTAATTCACGAAATATCTAAGATGGTCATCAAGTATAATGCCATTATTGCGA TGGAAGATCTGTCCTACGGATTTAAGAAAGGCAGGTTTAAAGTCGAAAGGCAGGTG TACCAGAAATTCGAGACCATGCTGATTAATAAGCTCAACTATCTCGTATTTAAGGAT ATTTCTATAACTGAAAATGGAGGGCTTCTCAAAGGATATCAACTCACATACATACCT GATAAGCTGAAGAACGTAGGCCACCAGTGTGGATGCATATTCTATGTACCAGCTGC ATACACAAGCAAGATCGATCCAACTACTGGGTTTGTCAATATCTTCAAATTTAAGGA CTTGACGGTCGATGCCAAACGGGAGTTCATCAAAAAGTTTGATAGTATTCGATATGA TAGTGAGAAGAACTTGTTTTGCTTCACATTTGACTACAACAATTTCATAACGCAAAA TACGGTTATGTCTAAATCCTCATGGAGCGTCTACACTTACGGAGTGAGGATAAAGCG GCGCTTCGTAAATGGCAGGTTTAGCAATGAATCCGACACGATTGACATAACCAAGG ATATGGAGAAAACCCTCGAGATGACCGATATAAATTGGCGGGATGGACACGATCTG CGACAAGACATAATCGATTATGAAATCGTGCAGCACATATTTGAGATATTCAGGCTT ACGGTCCAAATGAGAAATTCCCTTTCCGAACTTGAAGACCGCGATTACGACCGACTG ATAAGCCCCGTTCTGAACGAAAATAACATCTTCTACGACAGCGCTAAAGCGGGAGA CGCGCTGCCGAAAGATGCGGACGCAAATGGAGCCTATTGTATCGCCTTGAAAGGGT TGTACGAGATCAAACAGATAACCGAGAATTGGAAGGAGGATGGGAAGTTTAGTCGA GACAAACTTAAAATAAGCAACAAGGACTGGTTCGACTTTATTCAAAACAAACGATA TCTC SEQ ID NO: 41 ATGAATAATGGTACTAACAATTTTCAAAACTTTATCGGCATCTCTTCACTTCAGAAA ACTCTTCGGAACGCCCTTATACCGACGGAGACAACGCAGCAGTTTATAGTTAAAAAC GGGATCATTAAAGAAGATGAACTCAGAGGGGAAAACAGGCAAATATTGAAGGACA TTATGGACGATTACTACCGGGGGTTTATTTCAGAGACCCTTTCATCTATTGATGACAT AGATTGGACCTCCCTTTTCGAGAAAATGGAGATACAATTGAAAAACGGCGACAATA AAGATACACTTATCAAGGAACAAACTGAGTATCGCAAGGCGATTCACAAGAAGTTT GCGAATGACGATCGCTTTAAGAATATGTTTTCTGCGAAGCTCATAAGTGACATTCTG CCTGAATTTGTCATTCATAACAACAATTATTCTGCTAGCGAAAAAGAGGAAAAAACT CAAGTCATTAAGCTTTTTAGCAGGTTCGCTACTAGTTTTAAAGACTATTTTAAGAACC GGGCGAATTGCTTTAGCGCTGACGACATATCATCCTCATCCTGTCATCGCATAGTCA ATGATAATGCAGAAATATTCTTTTCTAATGCGCTCGTGTATCGGAGAATAGTGAAAA GCCTCTCTAACGATGACATTAACAAAATAAGCGGCGATATGAAGGATAGTCTGAAG GAAATGTCCCTCGAAGAAATATACTCATACGAGAAGTACGGAGAATTTATCACCCA GGAAGGAATTAGTTTTTACAACGACATCTGTGGTAAGGTTAACTCTTTTATGAATCT GTATTGTCAAAAGAATAAAGAAAATAAAAATCTTTATAAGCTCCAAAAGCTTCACA AACAAATCTTGTGCATTGCGGATACGTCATACGAAGTACCTTACAAATTTGAAAGCG ACGAAGAGGTGTATCAGTCAGTGAATGGGTTCCTTGACAATATTTCTAGCAAACATA TTGTGGAGCGACTTCGAAAGATCGGTGATAATTACAATGGCTATAATTTGGATAAAA TTTACATAGTTAGTAAGTTTTATGAATCCGTCTCACAAAAGACGTACCGAGATTGGG AGACCATCAACACTGCTCTGGAGATTCATTACAATAATATATTGCCTGGGAATGGGA AGTCAAAGGCCGACAAGGTTAAAAAAGCCGTAAAAAACGATCTTCAAAAGTCCATT ACCGAGATAAATGAACTTGTATCCAACTATAAGTTGTGCTCTGACGATAATATTAAA GCAGAAACGTATATCCACGAAATAAGTCACATCCTGAACAACTTCGAAGCTCAAGA GCTCAAGTATAATCCTGAAATTCATCTCGTCGAAAGCGAGCTGAAAGCATCCGAGTT GAAGAATGTGCTTGATGTGATCATGAACGCATTCCATTGGTGCAGTGTGTTCATGAC CGAAGAACTTGTAGACAAAGACAACAACTTCTACGCTGAATTGGAAGAGATTTACG ATGAAATTTACCCCGTGATATCCCTCTATAATCTGGTAAGAAATTACGTCACGCAAA AACCATACAGTACCAAGAAAATAAAGCTCAACTTTGGTATTCCGACGTTGGCAGAT GGGTGGAGTAAGAGCAAGGAGTATTCTAACAATGCAATCATCCTCATGCGCGACAA TTTGTATTATCTGGGGATCTTCAACGCGAAAAATAAGCCCGACAAAAAGATAATAG AAGGCAATACGTCCGAGAACAAAGGGGACTATAAGAAAATGATTTATAACCTTCTT CCAGGACCCAACAAGATGATCCCAAAGGTTTTCTTGAGTTCAAAAACCGGCGTAGA AACTTATAAACCGTCCGCCTACATTCTGGAAGGGTACAAGCAAAACAAGCACATTA AGTCATCTAAGGATTTCGACATTACTTTTTGTCATGATTTGATAGACTACTTCAAAAA TTGTATAGCGATACATCCGGAATGGAAAAATTTTGGGTTCGATTTTTCCGACACAAG TACTTATGAAGACATCTCAGGGTTTTATAGGGAAGTTGAACTGCAAGGTTACAAAAT AGACTGGACTTATATTAGTGAGAAGGACATTGATTTGCTCCAGGAAAAGGGTCAATT GTATCTGTTCCAGATATATAACAAGGATTTCTCTAAAAAATCTACAGGTAACGACAA TCTCCACACGATGTACCTCAAGAATCTCTTCAGCGAAGAGAATTTGAAGGATATCGT ACTTAAGCTCAATGGAGAAGCGGAAATATTCTTCAGAAAGTCCAGCATTAAGAATC CTATAATTCACAAGAAAGGGTCAATTCTCGTAAACCGGACTTATGAGGCCGAAGAA AAAGATCAGTTTGGTAACATTCAGATTGTACGGAAAAACATTCCCGAGAACATCTAT CAAGAACTGTATAAATACTTTAATGATAAATCCGACAAGGAACTTTCTGACGAGGCT GCAAAATTGAAGAACGTAGTGGGACACCATGAGGCCGCAACCAATATAGTAAAGGA TTACAGATACACTTATGATAAGTATTTCCTCCATATGCCGATCACGATTAATTTCAAG GCGAATAAAACCGGCTTCATTAACGATCGCATTTTGCAATATATTGCGAAGGAAAA GGATTTGCACGTGATAGGTATAGACCGGGGTGAACGAAACTTGATTTACGTCTCTGT GATCGACACATGCGGAAATATAGTTGAACAGAAGTCCTTTAATATTGTGAATGGTTA CGACTACCAGATAAAATTGAAGCAACAGGAGGGCGCAAGACAGATAGCTCGCAAA GAGTGGAAGGAAATCGGCAAGATCAAAGAAATAAAGGAGGGTTATCTTTCCCTGGT AATTCATGAAATTAGCAAGATGGTTATTAAGTATAATGCTATAATAGCTATGGAGGA CCTTTCCTATGGGTTCAAGAAAGGTCGCTTCAAAGTGGAGCGACAAGTGTATCAAAA GTTCGAGACTATGTTGATAAATAAATTGAATTATTTGGTTTTTAAAGACATTTCAATA ACTGAGAACGGGGGTCTCTTGAAGGGGTACCAATTGACTTATATTCCGGACAAGTTG AAGAATGTCGGACACCAGTGTGGTTGCATTTTCTACGTGCCTGCCGCTTACACCTCA AAAATCGATCCGACCACTGGTTTTGTAAATATATTTAAATTCAAAGATCTCACCGTT GATGCCAAACGGGAGTTTATCAAAAAATTCGATTCCATTCGCTACGACTCTGAGAAA AACCTTTTTTGTTTCACGTTCGATTATAACAACTTTATAACCCAAAATACTGTAATGT CCAAGTCAAGTTGGTCTGTCTATACTTACGGAGTAAGGATCAAGCGCCGCTTCGTTA ATGGGAGATTCTCAAACGAGTCTGATACCATAGACATAACTAAAGACATGGAAAAA ACCCTGGAAATGACGGACATCAATTGGCGAGACGGGCATGATCTTCGACAGGACAT AATAGATTACGAAATTGTTCAACACATTTTCGAGATATTTCGACTTACGGTTCAGAT GAGGAATTCCCTTTCCGAATTGGAAGACCGGGATTATGATCGACTTATATCTCCCGT GCTCAATGAAAACAATATTTTTTATGATTCAGCGAAAGCTGGGGACGCGCTGCCAAA AGATGCCGATGCCAATGGAGCATACTGTATCGCCCTGAAGGGTTTGTATGAGATTAA GCAAATTACTGAAAACTGGAAGGAAGATGGCAAGTTTTCTAGAGATAAGCTTAAGA TTAGCAATAAGGACTGGTTTGACTTCATTCAAAATAAAAGGTATCTT SEQ ID NO: 42 ATGAATAATGGAACAAATAATTTTCAAAATTTTATTGGTATCAGTTCATTGCAAAAG ACTTTGAGAAATGCTTTGATCCCGACTGAGACCACACAGCAGTTCATCGTCAAAAAT GGCATAATCAAGGAAGACGAACTTAGGGGTGAGAATAGACAAATATTGAAGGACAT CATGGATGACTATTATAGGGGGTTCATTTCCGAAACGCTCAGTAGTATTGATGACAT TGACTGGACTAGTCTTTTCGAGAAAATGGAAATTCAGCTTAAGAACGGGGACAATA AAGACACGCTGATCAAGGAGCAAACGGAATATAGGAAGGCGATCCATAAAAAATTC GCGAATGATGATCGGTTTAAAAACATGTTTAGTGCCAAGTTGATCAGCGACATACTG CCCGAATTCGTGATCCACAACAATAATTACAGCGCCTCCGAAAAGGAGGAAAAAAC TCAGGTCATTAAATTGTTTAGCCGATTCGCAACGAGTTTCAAAGATTATTTTAAGAA CCGGGCCAACTGTTTTTCAGCGGATGATATTAGCTCCAGCAGCTGCCATCGCATAGT AAATGATAACGCTGAAATCTTTTTTAGCAACGCACTTGTCTACCGGAGGATTGTAAA ATCACTGTCAAATGATGACATTAACAAAATATCTGGAGATATGAAGGACTCACTCA AAGAAATGAGCCTGGAAGAAATATATTCATACGAAAAATACGGGGAGTTTATTACC CAGGAAGGTATCAGTTTTTATAATGATATATGTGGAAAAGTTAATTCATTTATGAAT CTTTACTGTCAAAAAAATAAGGAGAACAAGAATTTGTACAAGCTCCAAAAACTTCA TAAACAGATTCTGTGCATCGCAGACACAAGTTATGAGGTACCGTACAAATTTGAGA GCGACGAAGAAGTTTATCAGAGTGTGAATGGTTTCCTGGACAATATCTCTTCTAAAC ACATTGTTGAGAGGCTTAGGAAGATCGGTGATAATTATAACGGCTATAATCTGGACA AAATTTATATTGTATCAAAGTTTTATGAATCAGTCTCTCAAAAGACGTATCGGGATT GGGAAACAATTAACACGGCTCTGGAGATCCACTACAATAACATTCTGCCCGGCAAC GGGAAGAGCAAAGCTGATAAGGTCAAGAAGGCAGTCAAGAACGACCTTCAGAAGA GCATAACAGAAATTAACGAATTGGTCAGTAACTACAAACTGTGTAGTGATGACAAC ATAAAAGCCGAAACATACATCCATGAAATAAGCCATATCCTGAATAACTTCGAAGC CCAAGAACTTAAATACAATCCCGAGATTCATCTTGTCGAATCAGAACTCAAGGCGTC CGAGCTCAAAAATGTCCTTGACGTGATAATGAATGCCTTCCACTGGTGCAGCGTATT CATGACGGAGGAGTTGGTAGATAAAGACAACAACTTTTATGCCGAATTGGAAGAGA TTTATGATGAGATTTACCCCGTTATTTCTCTGTACAACTTGGTTCGAAACTACGTAAC ACAAAAACCATACTCAACCAAAAAGATCAAACTCAATTTTGGCATACCTACATTGGC TGATGGTTGGTCCAAGTCAAAGGAATATAGCAATAATGCAATAATTCTCATGCGAG ATAACTTGTATTATTTGGGGATCTTTAACGCTAAGAACAAACCAGATAAAAAGATAA TCGAGGGGAACACAAGTGAGAACAAGGGTGATTACAAAAAAATGATTTACAATCTG CTTCCTGGGCCTAACAAAATGATTCCGAAGGTGTTTCTTAGCTCTAAAACTGGAGTG GAGACGTATAAGCCTTCCGCGTACATTCTCGAAGGCTACAAGCAAAATAAGCATAT CAAGTCCAGTAAGGACTTCGACATCACTTTTTGCCACGATCTCATCGATTACTTTAA GAACTGTATCGCAATACACCCCGAGTGGAAAAACTTTGGTTTTGATTTTTCAGACAC TAGTACCTACGAGGACATTTCCGGCTTCTATCGAGAAGTCGAACTCCAGGGCTACAA AATCGATTGGACGTACATTTCTGAGAAGGACATCGACTTGCTCCAAGAGAAAGGTC AACTTTACCTCTTCCAAATTTACAATAAAGACTTTTCAAAGAAGAGCACCGGTAATG ACAACTTGCATACCATGTATCTGAAGAACCTGTTTTCTGAGGAGAACCTCAAGGATA TTGTATTGAAGTTGAATGGCGAAGCAGAAATATTTTTCCGAAAGTCATCTATCAAGA ACCCCATTATACACAAAAAAGGCTCTATCCTGGTGAACCGGACTTACGAGGCAGAG GAGAAGGATCAATTCGGAAACATACAGATAGTCCGCAAAAACATCCCTGAGAATAT CTATCAGGAACTCTATAAGTACTTCAATGATAAATCAGACAAGGAGCTTAGCGACG AAGCAGCTAAACTTAAAAACGTGGTTGGCCATCACGAGGCCGCTACCAACATAGTC AAAGACTACCGCTATACTTATGACAAGTACTTTTTGCACATGCCCATAACAATTAAT TTCAAAGCTAACAAAACAGGGTTTATAAATGACAGAATCCTCCAATACATCGCCAA AGAGAAGGACCTCCATGTAATCGGGATTGATAGAGGCGAACGGAACTTGATTTACG TTAGTGTCATTGATACCTGTGGTAACATTGTCGAACAAAAGTCATTCAACATAGTCA ATGGATATGATTATCAGATAAAACTCAAGCAACAAGAAGGCGCGAGGCAGATTGCC AGGAAGGAATGGAAAGAAATCGGGAAGATCAAGGAGATCAAGGAGGGTTACCTGT CCTTGGTGATACACGAGATTTCAAAAATGGTTATAAAATACAATGCCATTATCGCGA TGGAGGATTTGTCTTATGGATTTAAGAAGGGGAGGTTCAAAGTCGAACGACAAGTC TATCAGAAGTTTGAAACAATGCTCATTAACAAGCTCAATTACCTTGTTTTCAAGGAT ATAAGCATCACTGAAAACGGCGGACTCCTTAAGGGATATCAGCTGACTTATATCCCC GACAAGCTCAAGAACGTAGGGCACCAATGCGGATGCATCTTTTACGTGCCTGCAGC ATATACTTCAAAAATTGATCCGACTACTGGCTTTGTTAACATTTTCAAGTTCAAGGAT CTGACGGTAGACGCTAAGAGAGAATTCATAAAAAAGTTTGACAGCATCAGGTACGA TAGTGAAAAGAACCTTTTTTGTTTTACCTTTGACTACAATAATTTTATTACGCAAAAT ACAGTTATGAGCAAATCAAGTTGGAGCGTTTACACATATGGCGTTCGGATCAAGCGC AGATTCGTCAATGGTCGCTTCTCAAATGAGAGCGATACAATCGATATAACGAAGGA TATGGAGAAGACGCTTGAGATGACAGATATCAACTGGCGGGACGGACATGACCTTA GACAAGACATAATCGATTACGAAATAGTACAGCATATCTTTGAGATTTTTAGGCTTA CAGTTCAGATGCGGAACTCTCTTTCCGAACTGGAGGACCGGGATTATGATCGGTTGA TCTCCCCAGTACTGAACGAAAATAATATCTTTTACGATAGCGCGAAGGCTGGTGATG CACTCCCAAAAGACGCTGATGCGAACGGAGCTTATTGCATAGCCCTTAAAGGGCTTT ACGAGATTAAACAAATAACAGAAAATTGGAAGGAAGATGGCAAATTTTCCCGCGAC AAGTTGAAGATTAGTAACAAAGACTGGTTCGACTTCATTCAGAATAAACGCTACCTC

Nucleic acid-guided nucleases can encompass a native sequence, an engineered sequence, or engineered nucleotide sequences of synthetized variants. Non-limiting examples of types of engineering that can be done to obtain a non-naturally occurring nuclease system are as follows. Engineering can include codon optimization to facilitate expression or improve expression in a host cell, such as a heterologous host cell. Engineering can reduce the size or molecular weight of the nuclease in order to facilitate expression or delivery. Engineering can alter PAM selection in order to change PAM specificity or to broaden the range of recognized PAMs. Engineering can alter, increase, or decrease stability, processivity, specificity, or efficiency of a targetable nuclease system. Engineering can alter, increase, or decrease protein stability. Engineering can alter, increase, or decrease processivity of nucleic acid scanning. Engineering can alter, increase, or decrease target sequence specificity. Engineering can alter, increase, or decrease nuclease activity. Engineering can alter, increase, or decrease editing efficiency. Engineering can alter, increase, or decrease transformation efficiency. Engineering can alter, increase, or decrease nuclease or guide nucleic acid expression. As used herein, a non-naturally occurring nucleic acid sequence can be an engineered sequence or engineered nucleotide sequences of synthetized variants. Such non-naturally occurring nucleic acid sequences can be amplified, cloned, assembled, synthesized, generated from synthesized oligonucleotides or dNTPs, or otherwise obtained using methods known by those skilled in the art. In certain embodiments, examples of non-naturally occurring nucleic acid-guided nucleases disclosed herein can include those nucleic acid-guided nucleases with engineered polypeptide sequences (e.g., SEQ ID NOs:2-4) and those nucleotide sequences of synthetized variants (e.g., SEQ ID NOs: 43-63).

SEQ ID NO: 2 MGHHHHHHSSGVDLGTENLYFQSPAAKKKKLDGSVDMNNGTNNFQNFIGISSLQKTLR NALIPTETTQQFIVKNGIIKEDELRGENRQILKDIMDDYYRGFISETLSSIDDIDWTSLFEK MEIQLKNGDNKDTLIKEQTEYRKAIHKKFANDDRFKNMFSAKLISDILPEFVIHNNNYSA SEKEEKTQVIKLFSRFATSFKDYFKNRANCFSADDISSSSCHRIVNDNAEIFFSNALVYRRI VKSLSNDDINKISGDMKDSLKEMSLEEIYSYEKYGEFITQEGISFYNDICGKVNSFMNLY CQKNKENKNLYKLQKLHKQILCIADTSYEVPYKFESDEEVYQSVNGFLDNISSKHIVERL RKIGDNYNGYNLDKIYIVSKFYESVSQKTYRDWETINTALEIHYNNILPGNGKSKADKV KKAVKNDLQKSITEINELVSNYKLCSDDNIKAETYIHEISHILNNFEAQELKYNPEIHLVE SELKASELKNVLDVIMNAFHWCSVFMTEELVDKDNNFYAELEEIYDEIYPVISLYNLVR NYVTQKPYSTKKIKLNFGIPTLADGWSKSKEYSNNAIILMRDNLYYLGIFNAKNKPDKKI IEGNTSENKGDYKKMIYNLLPGPNKMIPKVFLSSKTGVETYKPSAYILEGYKQNKHIKSS KDFDITFCHDLIDYFKNCIAIHPEWKNFGFDFSDTSTYEDISGFYREVELQGYKIDWTYIS EKDIDLLQEKGQLYLFQIYNKDFSKKSTGNDNLHTMYLKNLFSEENLKDIVLKLNGEAEI FFRKSSIKNPIIHKKGSILVNRTYEAEEKDQFGNIQIVRKNIPENIYQELYKYFNDKSDKEL SDEAAKLKNVVGHHEAATNIVKDYRYTYDKYFLHMPITINFKANKTGFINDRILQYIAK EKDLHVIGIDRGERNLIYVSVIDTCGNIVEQKSFNIVNGYDYQIKLKQQEGARQIARKEW KEIGKIKEIKEGYLSLVIHEISKMVIKYNAIIAMEDLSYGFKKGRFKVERQVYQKFETMLI NKLNYLVFKDISITENGGLLKGYQLTYIPDKLKNVGHQCGCIFYVPAAYTSKIDPTTGFV NIFKFKDLTVDAKREFIKKFDSIRYDSEKNLFCFTFDYNNFITQNTVMSKSSWSVYTYGV RIKRRFVNGRFSNESDTIDITKDMEKTLEMTDINWRDGHDLRQDIIDYEIVQHIFEIFRLTV QMRNSLSELEDRDYDRLISPVLNENNIFYDSAKAGDALPKDADANGAYCIALKGLYEIK QITENWKEDGKFSRDKLKISNKDWFDFIQNKRYLKRPAATKKAGQAKKKKASGSGAGS PKKKRKVEDPKKKRKVIPG* SEQ ID NO: 3 SPAAKKKKLDGSVDMNNGTNNFQNFIGISSLQKTLRNALIPTETTQQFIVKNGIIKEDELR GENRQILKDIMDDYYRGFISETLSSIDDIDWTSLFEKMEIQLKNGDNKDTLIKEQTEYRK AIHKKFANDDRFKNMFSAKLISDILPEFVIHNNNYSASEKEEKTQVIKLFSRFATSFKDYF KNRANCFSADDISSSSCHRIVNDNAEIFFSNALVYRRIVKSLSNDDINKISGDMKDSLKEM SLEEIYSYEKYGEFITQEGISFYNDICGKVNSFMNLYCQKNKENKNLYKLQKLHKQILCI ADTSYEVPYKFESDEEVYQSVNGFLDNISSKHIVERLRKIGDNYNGYNLDKIYIVSKFYE SVSQKTYRDWETINTALEIHYNNILPGNGKSKADKVKKAVKNDLQKSITEINELVSNYK LCSDDNIKAETYIHEISHILNNFEAQELKYNPEIHLVESELKASELKNVLDVIMNAFHWCS VFMTEELVDKDNNFYAELEEIYDEIYPVISLYNLVRNYVTQKPYSTKKIKLNFGIPTLAD GWSKSKEYSNNAIILMRDNLYYLGIFNAKNKPDKKIIEGNTSENKGDYKKMIYNLLPGP NKMIPKVFLSSKTGVETYKPSAYILEGYKQNKHIKSSKDFDITFCHDLIDYFKNCIAIHPE WKNFGFDFSDTSTYEDISGFYREVELQGYKIDWTYISEKDIDLLQEKGQLYLFQIYNKDF SKKSTGNDNLHTMYLKNLFSEENLKDIVLKLNGEAEIFFRKSSIKNPIIHKKGSILVNRTY EAEEKDQFGNIQIVRKNIPENIYQELYKYFNDKSDKELSDEAAKLKNVVGHHEAATNIV KDYRYTYDKYFLHMPITINFKANKTGFINDRILQYIAKEKDLHVIGIDRGERNLIYVSVID TCGNIVEQKSFNIVNGYDYQIKLKQQEGARQIARKEWKEIGKIKEIKEGYLSLVIHEISKM VIKYNAIIAMEDLSYGFKKGRFKVERQVYQKFETMLINKLNYLVFKDISITENGGLLKGY QLTYIPDKLKNVGHQCGCIFYVPAAYTSKIDPTTGFVNIFKFKDLTVDAKREFIKKFDSIR YDSEKNLFCFTFDYNNFITQNTVMSKSSWSVYTYGVRIKRRFVNGRFSNESDTIDITKDM EKTLEMTDINWRDGHDLRQDIIDYEIVQHIFEIFRLTVQMRNSLSELEDRDYDRLISPVLN ENNIFYDSAKAGDALPKDADANGAYCIALKGLYEIKQITENWKEDGKFSRDKLKISNKD WFDFIQNKRYLKRPAATKKAGQAKKKKASGSGAGSPKKKRKVEDPKKKRKVIPG* SEQ ID NO: 4 PAAKKKKLDGSVDMNNGTNNFQNFIGISSLQKTLRNALIPTETTQQFIVKNGIIKEDELRG ENRQILKDIMDDYYRGFISETLSSIDDIDWTSLFEKMEIQLKNGDNKDTLIKEQTEYRKAI HKKFANDDRFKNMFSAKLISDILPEFVIHNNNYSASEKEEKTQVIKLFSRFATSFKDYFK NRANCFSADDISSSSCHRIVNDNAEIFFSNALVYRRIVKSLSNDDINKISGDMKDSLKEMS LEEIYSYEKYGEFITQEGISFYNDICGKVNSFMNLYCQKNKENKNLYKLQKLHKQILCIA DTSYEVPYKFESDEEVYQSVNGFLDNISSKHIVERLRKIGDNYNGYNLDKIYIVSKFYES VSQKTYRDWETINTALEIHYNNILPGNGKSKADKVKKAVKNDLQKSITEINELVSNYKL CSDDNIKAETYIHEISHILNNFEAQELKYNPEIHLVESELKASELKNVLDVIMNAFHWCSV FMTEELVDKDNNFYAELEEIYDEIYPVISLYNLVRNYVTQKPYSTKKIKLNFGIPTLADG WSKSKEYSNNAIILMRDNLYYLGIFNAKNKPDKKIIEGNTSENKGDYKKMIYNLLPGPN KMIPKVFLSSKTGVETYKPSAYILEGYKQNKHIKSSKDFDITFCHDLIDYFKNCIAIHPEW KNFGFDFSDTSTYEDISGFYREVELQGYKIDWTYISEKDIDLLQEKGQLYLFQIYNKDFSK KSTGNDNLHTMYLKNLFSEENLKDIVLKLNGEAEIFFRKSSIKNPIIHKKGSILVNRTYEA EEKDQFGNIQIVRKNIPENIYQELYKYFNDKSDKELSDEAAKLKNVVGHHEAATNIVKD YRYTYDKYFLHMPITINFKANKTGFINDRILQYIAKEKDLHVIGIDRGERNLIYVSVIDTC GNIVEQKSFNIVNGYDYQIKLKQQEGARQIARKEWKEIGKIKEIKEGYLSLVIHEISKMVI KYNAIIAMEDLSYGFKKGRFKVERQVYQKFETMLINKLNYLVFKDISITENGGLLKGYQ LTYIPDKLKNVGHQCGCIFYVPAAYTSKIDPTTGFVNIFKFKDLTVDAKREFIKKFDSIRY DSEKNLFCFTFDYNNFITQNTVMSKSSWSVYTYGVRIKRRFVNGRFSNESDTIDITKDME KTLEMTDINWRDGHDLRQDIIDYEIVQHIFEIFRLTVQMRNSLSELEDRDYDRLISPVLNE NNIFYDSAKAGDALPKDADANGAYCIALKGLYEIKQITENWKEDGKFSRDKLKISNKD WFDFIQNKRYLKRPAATKKAGQAKKKKASGSGAGSPKKKRKVEDPKKKRKVIPG* SEQ ID NO: 109: SMSRRRKANPTKLSENAKKLAKEVENASGSGAGSKRPAATKKAGQAKKKKASGSGAG SPAAKKKKLDGSVDASGSGAGSPKKKRKVEDASGSGAGSPKKKRKVASGSGAGSMNN GTNNFQNFIGISSLQKTLRNALIPTETTQQFIVKNGIIKEDELRGENRQILKDIMDDYYRGF ISETLSSIDDIDWTSLFEKMEIQLKNGDNKDTLIKEQTEYRKAIHKKFANDDRFKNMFSA KLISDILPEFVIHNNNYSASEKEEKTQVIKLFSRFATSFKDYFKNRANCFSADDISSSSCHR IVNDNAEIFFSNALVYRRIVKSLSNDDINKISGDMKDSLKEMSLEEIYSYEKYGEFITQEGI SFYNDICGKVNSFMNLYCQKNKENKNLYKLQKLHKQILCIADTSYEVPYKFESDEEVYQ SVNGFLDNISSKHIVERLRKIGDNYNGYNLDKIYIVSKFYESVSQKTYRDWETINTALEIH YNNILPGNGKSKADKVKKAVKNDLQKSITEINELVSNYKLCSDDNIKAETYIHEISHILN NFEAQELKYNPEIHLVESELKASELKNVLDVIMNAFHWCSVFMTEELVDKDNNFYAELE EIYDEIYPVISLYNLVRNYVTQKPYSTKKIKLNFGIPTLADGWSKSKEYSNNAIILMRDNL YYLGIFNAKNKPDKKIIEGNTSENKGDYKKMIYNLLPGPNKMIPKVFLSSKTGVETYKPS AYILEGYKQNKHIKSSKDFDITFCHDLIDYFKNCIAIHPEWKNFGFDFSDTSTYEDISGFY REVELQGYKIDWTYISEKDIDLLQEKGQLYLFQIYNKDFSKKSTGNDNLHTMYLKNLFS EENLKDIVLKLNGEAEIFFRKSSIKNPIIHKKGSILVNRTYEAEEKDQFGNIQIVRKNIPENI YQELYKYFNDKSDKELSDEAAKLKNVVGHHEAATNIVKDYRYTYDKYFLHMPITINFK ANKTGFINDRILQYIAKEKDLHVIGIDRGERNLIYVSVIDTCGNIVEQKSFNIVNGYDYQI KLKQQEGARQIARKEWKEIGKIKEIKEGYLSLVIHEISKMVIKYNAIIAMEDLSYGFKKG RFKVERQVYQKFETMLINKLNYLVFKDISITENGGLLKGYQLTYIPDKLKNVGHQCGCIF YVPAAYTSKIDPTTGFVNIFKFKDLTVDAKREFIKKFDSIRYDSEKNLFCFTFDYNNFITQ NTVMSKSSWSVYTYGVRIKRRFVNGRFSNESDTIDITKDMEKTLEMTDINWRDGHDLR QDIIDYEIVQHIFEIFRLTVQMRNSLSELEDRDYDRLISPVLNENNIFYDSAKAGDALPKD ADANGAYCIALKGLYEIKQITENWKEDGKFSRDKLKISNKDWFDFIQNKRYL SEQ ID NO: 110: MSRRRKANPTKLSENAKKLAKEVENASGSGAGSKRPAATKKAGQAKKKKASGSGAGS PAAKKKKLDGSVDASGSGAGSPKKKRKVEDASGSGAGSPKKKRKVASGSGAGSMNNG TNNFQNFIGISSLQKTLRNALIPTETTQQFIVKNGIIKEDELRGENRQILKDIMDDYYRGFI SETLSSIDDIDWTSLFEKMEIQLKNGDNKDTLIKEQTEYRKAIHKKFANDDRFKNMFSAK LISDILPEFVIHNNNYSASEKEEKTQVIKLFSRFATSFKDYFKNRANCFSADDISSSSCHRI VNDNAEIFFSNALVYRRIVKSLSNDDINKISGDMKDSLKEMSLEEIYSYEKYGEFITQEGI SFYNDICGKVNSFMNLYCQKNKENKNLYKLQKLHKQILCIADTSYEVPYKFESDEEVYQ SVNGFLDNISSKHIVERLRKIGDNYNGYNLDKIYIVSKFYESVSQKTYRDWETINTALEIH YNNILPGNGKSKADKVKKAVKNDLQKSITEINELVSNYKLCSDDNIKAETYIHEISHILN NFEAQELKYNPEIHLVESELKASELKNVLDVIMNAFHWCSVFMTEELVDKDNNFYAELE EIYDEIYPVISLYNLVRNYVTQKPYSTKKIKLNFGIPTLADGWSKSKEYSNNAIILMRDNL YYLGIFNAKNKPDKKIIEGNTSENKGDYKKMIYNLLPGPNKMIPKVFLSSKTGVETYKPS AYILEGYKQNKHIKSSKDFDITFCHDLIDYFKNCIAIHPEWKNFGFDFSDTSTYEDISGFY REVELQGYKIDWTYISEKDIDLLQEKGQLYLFQIYNKDFSKKSTGNDNLHTMYLKNLFS EENLKDIVLKLNGEAEIFFRKSSIKNPIIHKKGSILVNRTYEAEEKDQFGNIQIVRKNIPENI YQELYKYFNDKSDKELSDEAAKLKNVVGHHEAATNIVKDYRYTYDKYFLHMPITINFK ANKTGFINDRILQYIAKEKDLHVIGIDRGERNLIYVSVIDTCGNIVEQKSFNIVNGYDYQI KLKQQEGARQIARKEWKEIGKIKEIKEGYLSLVIHEISKMVIKYNAIIAMEDLSYGFKKG RFKVERQVYQKFETMLINKLNYLVFKDISITENGGLLKGYQLTYIPDKLKNVGHQCGCIF YVPAAYTSKIDPTTGFVNIFKFKDLTVDAKREFIKKFDSIRYDSEKNLFCFTFDYNNFITQ NTVMSKSSWSVYTYGVRIKRRFVNGRFSNESDTIDITKDMEKTLEMTDINWRDGHDLR QDIIDYEIVQHIFEIFRLTVQMRNSLSELEDRDYDRLISPVLNENNIFYDSAKAGDALPKD ADANGAYCIALKGLYEIKQITENWKEDGKFSRDKLKISNKDWFDFIQNKRYL SEQ ID NO: 111 GHHHHHHSSGVDLGTENLYFQSMSRRRKANPTKLSENAKKLAKEVENASGSGAGSKRP AATKKAGQAKKKKASGSGAGSPAAKKKKLDGSVDASGSGAGSPKKKRKVEDASGSGA GSPKKKRKVASGSGAGSMNNGTNNFQNFIGISSLQKTLRNALIPTETTQQFIVKNGIIKED ELRGENRQILKDIMDDYYRGFISETLSSIDDIDWTSLFEKMEIQLKNGDNKDTLIKEQTEY RKAIHKKFANDDRFKNMFSAKLISDILPEFVIHNNNYSASEKEEKTQVIKLFSRFATSFKD YFKNRANCFSADDISSSSCHRIVNDNAEIFFSNALVYRRIVKSLSNDDINKISGDMKDSLK EMSLEEIYSYEKYGEFITQEGISFYNDICGKVNSFMNLYCQKNKENKNLYKLQKLHKQIL CIADTSYEVPYKFESDEEVYQSVNGFLDNISSKHIVERLRKIGDNYNGYNLDKIYIVSKFY ESVSQKTYRDWETINTALEIHYNNILPGNGKSKADKVKKAVKNDLQKSITEINELVSNY KLCSDDNIKAETYIHEISHILNNFEAQELKYNPEIHLVESELKASELKNVLDVIMNAFHW CSVFMTEELVDKDNNFYAELEEIYDEIYPVISLYNLVRNYVTQKPYSTKKIKLNFGIPTLA DGWSKSKEYSNNAIILMRDNLYYLGIFNAKNKPDKKIIEGNTSENKGDYKKMIYNLLPG PNKMIPKVFLSSKTGVETYKPSAYILEGYKQNKHIKSSKDFDITFCHDLIDYFKNCIAIHPE WKNFGFDFSDTSTYEDISGFYREVELQGYKIDWTYISEKDIDLLQEKGQLYLFQIYNKDF SKKSTGNDNLHTMYLKNLFSEENLKDIVLKLNGEAEIFFRKSSIKNPIIHKKGSILVNRTY EAEEKDQFGNIQIVRKNIPENIYQELYKYFNDKSDKELSDEAAKLKNVVGHHEAATNIV KDYRYTYDKYFLHMPITINFKANKTGFINDRILQYIAKEKDLHVIGIDRGERNLIYVSVID TCGNIVEQKSFNIVNGYDYQIKLKQQEGARQIARKEWKEIGKIKEIKEGYLSLVIHEISKM VIKYNAIIAMEDLSYGFKKGRFKVERQVYQKFETMLINKLNYLVFKDISITENGGLLKGY QLTYIPDKLKNVGHQCGCIFYVPAAYTSKIDPTTGFVNIFKFKDLTVDAKREFIKKFDSIR YDSEKNLFCFTFDYNNFITQNTVMSKSSWSVYTYGVRIKRRFVNGRFSNESDTIDITKDM EKTLEMTDINWRDGHDLRQDIIDYEIVQHIFEIFRLTVQMRNSLSELEDRDYDRLISPVLN ENNIFYDSAKAGDALPKDADANGAYCIALKGLYEIKQITENWKEDGKFSRDKLKISNKD WFDFIQNKRYL* SEQ ID NO: 112 MGHHHHHHSSGVDLGTENLYFQSMSRRRKANPTKLSENAKKLAKEVENASGSGAGSK RPAATKKAGQAKKKKASGSGAGSPAAKKKKLDGSVDASGSGAGSPKKKRKVEDASGS GAGSPKKKRKVASGSGAGSMNNGTNNFQNFIGISSLQKTLRNALIPTETTQQFIVKNGIIK EDELRGENRQILKDIMDDYYRGFISETLSSIDDIDWTSLFEKMEIQLKNGDNKDTLIKEQT EYRKAIHKKFANDDRFKNMFSAKLISDILPEFVIHNNNYSASEKEEKTQVIKLFSRFATSF KDYFKNRANCFSADDISSSSCHRIVNDNAEIFFSNALVYRRIVKSLSNDDINKISGDMKDS LKEMSLEEIYSYEKYGEFITQEGISFYNDICGKVNSFMNLYCQKNKENKNLYKLQKLHK QILCIADTSYEVPYKFESDEEVYQSVNGFLDNISSKHIVERLRKIGDNYNGYNLDKIYIVS KFYESVSQKTYRDWETINTALEIHYNNILPGNGKSKADKVKKAVKNDLQKSITEINELVS NYKLCSDDNIKAETYIHEISHILNNFEAQELKYNPEIHLVESELKASELKNVLDVIMNAFH WCSVFMTEELVDKDNNFYAELEEIYDEIYPVISLYNLVRNYVTQKPYSTKKIKLNFGIPT LADGWSKSKEYSNNAIILMRDNLYYLGIFNAKNKPDKKIIEGNTSENKGDYKKMIYNLL PGPNKMIPKVFLSSKTGVETYKPSAYILEGYKQNKHIKSSKDFDITFCHDLIDYFKNCIAI HPEWKNFGFDFSDTSTYEDISGFYREVELQGYKIDWTYISEKDIDLLQEKGQLYLFQIYN KDFSKKSTGNDNLHTMYLKNLFSEENLKDIVLKLNGEAEIFFRKSSIKNPIIHKKGSILVN RTYEAEEKDQFGNIQIVRKNIPENIYQELYKYFNDKSDKELSDEAAKLKNVVGHHEAAT NIVKDYRYTYDKYFLHMPITINFKANKTGFINDRILQYIAKEKDLHVIGIDRGERNLIYVS VIDTCGNIVEQKSFNIVNGYDYQIKLKQQEGARQIARKEWKEIGHIKEIKEGYLSLVIHEI SKMVIKYNAIIAMEDLSYGFKKGRFKVERQVYQKFETMLINKLNYLVFKDISITENGGLL KGYQLTYIPDKLKNVGHQCGCIFYVPAAYTSKIDPTTGFVNIFKFKDLTVDAKREFIKKF DSIRYDSEKNLFCFTFDYNNFITQNTVMSKSSWSVYTYGVRIKRRFVNGRFSNESDTIDIT KDMEKTLEMTDINWRDGHDLRQDIIDYEIVQHIFEIFRLTVQMRNSLSELEDRDYDRLIS PVLNENNIFYDSAKAGDALPKDADANGAYCIALKGLYEIKQITENWKEDGKFSRDKLKI SNKDWFDFIQNKRYL* SEQ ID NO: 43 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA TAACGGTACCAATAACTTCCAGAACTTCATCGGTATTTCTAGCCTGCAAAAGACCCT GCGTAACGCGCTGATTCCGACCGAGACTACCCAGCAATTCATCGTGAAAAACGGTA TCATTAAGGAAGATGAATTGCGCGGTGAGAATCGTCAGATTCTGAAAGATATCATG GATGACTACTATCGCGGTTTCATTAGCGAAACCCTGTCGAGCATCGATGATATCGAT TGGACGAGCCTCTTCGAGAAAATGGAAATTCAACTGAAAAATGGTGACAACAAAGA TACCCTGATTAAAGAACAAACGGAATACCGCAAGGCAATCCATAAAAAGTTTGCGA ATGACGACCGTTTTAAGAATATGTTCTCGGCCAAGCTGATTTCCGACATCCTGCCAG AGTTCGTCATTCACAACAACAATTACAGCGCAAGCGAGAAAGAGGAAAAGACTCAG GTCATTAAGCTGTTTAGCCGCTTTGCGACGTCCTTCAAAGACTACTTCAAGAATCGT GCGAATTGCTTTAGCGCGGATGACATCTCTAGCTCTAGCTGTCACCGTATTGTTAAC GACAATGCAGAGATTTTCTTCAGCAACGCCCTGGTGTATCGCCGTATTGTCAAGTCT CTGAGCAACGACGACATTAACAAGATCAGCGGCGACATGAAAGACAGCCTGAAAG AAATGTCTCTGGAAGAAATCTACAGCTACGAGAAATATGGTGAGTTTATCACCCAA GAGGGCATTAGCTTCTACAATGATATCTGTGGTAAGGTTAATAGCTTTATGAATCTG TACTGCCAGAAGAATAAAGAAAACAAGAACTTGTACAAGCTGCAAAAGCTGCATAA GCAAATTCTGTGCATCGCCGATACTAGCTATGAAGTTCCGTACAAGTTCGAGTCTGA TGAAGAGGTGTATCAGTCAGTCAACGGTTTTCTGGATAACATCAGCAGCAAGCACAT CGTCGAGCGCCTGCGCAAGATTGGTGACAACTACAATGGTTATAACCTGGACAAGA TCTATATCGTGTCGAAGTTTTACGAGAGCGTGTCCCAGAAAACGTACCGTGATTGGG AAACGATTAACACGGCCTTGGAAATTCACTATAACAATATCCTGCCGGGCAACGGC AAGAGCAAAGCTGACAAAGTCAAAAAAGCTGTGAAAAACGATCTGCAAAAGTCCAT CACCGAGATCAACGAACTGGTTAGCAACTATAAGCTGTGTAGCGACGACAACATTA AAGCTGAAACGTATATCCACGAAATCAGCCACATCCTGAATAACTTTGAGGCACAA GAACTGAAATACAATCCTGAGATCCATCTGGTAGAGAGCGAGCTGAAGGCAAGCGA GTTGAAAAACGTTCTCGACGTTATCATGAATGCTTTCCACTGGTGTAGCGTGTTTATG ACCGAAGAACTGGTTGACAAAGATAACAATTTCTATGCAGAGCTGGAAGAAATCTA TGATGAAATCTACCCGGTCATCAGCCTGTATAACCTGGTTCGTAACTACGTGACGCA GAAGCCGTACAGCACCAAAAAGATCAAGCTGAACTTCGGTATTCCGACCTTGGCGG ACGGTTGGAGCAAATCCAAAGAATACTCCAATAATGCGATTATTCTGATGCGTGATA ATCTGTACTATCTGGGTATCTTCAATGCGAAGAACAAGCCAGATAAAAAGATTATTG AAGGCAACACCAGCGAGAATAAAGGCGACTACAAGAAAATGATCTACAACTTATTG CCGGGTCCGAACAAGATGATCCCGAAAGTTTTTCTGAGCAGCAAGACCGGCGTTGA AACCTATAAGCCGAGCGCGTACATTTTAGAGGGCTATAAACAAAACAAGCACATCA AGAGCAGCAAAGATTTTGATATTACGTTCTGCCACGACCTGATCGACTATTTCAAGA ATTGTATTGCGATTCACCCTGAGTGGAAGAACTTCGGTTTTGACTTTTCCGATACCTC CACCTATGAAGATATTAGCGGTTTTTACCGTGAAGTCGAGTTGCAGGGTTATAAGAT TGATTGGACTTACATTTCCGAGAAAGACATCGACCTGTTGCAAGAGAAAGGTCAGCT GTACCTGTTTCAGATCTATAACAAAGATTTCAGCAAAAAGTCGACGGGCAATGATA ATCTGCACACCATGTATCTGAAAAACCTGTTTAGCGAAGAGAACCTGAAAGACATT GTTCTTAAGCTGAATGGTGAGGCCGAGATCTTCTTCCGTAAAAGCTCCATTAAGAAC CCGATTATCCACAAAAAGGGCTCTATTCTGGTTAACCGCACGTACGAAGCGGAAGA GAAAGATCAATTTGGTAACATCCAGATCGTGCGTAAGAATATCCCGGAGAACATTT ACCAAGAACTGTATAAGTATTTCAATGACAAGAGCGATAAAGAATTGAGCGATGAA GCGGCAAAGCTGAAAAACGTCGTTGGCCACCACGAAGCCGCGACGAATATCGTGAA AGATTATCGTTACACCTACGACAAGTACTTTCTGCACATGCCGATCACCATCAATTT CAAAGCGAATAAAACGGGTTTTATCAATGACCGTATCCTGCAGTACATTGCGAAAG AAAAAGATTTACACGTGATTGGTATTGATCGCGGCGAGCGCAATCTGATTTACGTCA GCGTTATCGACACGTGCGGCAATATTGTGGAGCAGAAAAGCTTCAATATCGTCAATG GTTACGACTACCAGATCAAACTGAAGCAACAAGAGGGCGCCCGCCAGATTGCGCGT AAAGAGTGGAAAGAAATCGGTAAGATTAAAGAAATCAAGGAAGGCTACCTGTCCCT GGTGATCCATGAAATCAGCAAAATGGTGATCAAGTACAACGCTATCATTGCGATGG AAGATCTGAGCTACGGTTTTAAAAAGGGTCGCTTCAAAGTTGAGCGTCAAGTGTATC AGAAATTTGAGACTATGCTGATTAACAAGTTGAACTATCTGGTTTTTAAAGACATCA GCATTACCGAGAATGGTGGCCTGCTGAAGGGTTATCAACTGACCTATATTCCTGACA AGTTGAAAAATGTTGGTCATCAGTGTGGTTGCATTTTCTACGTACCGGCAGCGTACA CGAGCAAGATTGACCCGACCACGGGTTTCGTTAACATTTTCAAGTTTAAAGATTTGA CCGTGGACGCCAAGCGTGAGTTCATTAAAAAGTTCGACAGCATCAGATACGACTCT GAGAAGAATCTGTTCTGCTTTACGTTCGACTACAATAACTTCATTACCCAAAATACC GTTATGAGCAAAAGCTCCTGGAGCGTGTACACGTACGGCGTCCGTATCAAGCGTCGT TTTGTGAATGGTCGCTTTTCCAACGAATCTGACACCATTGACATTACCAAAGATATG GAAAAGACCCTTGAGATGACCGACATTAATTGGCGTGATGGCCATGACTTGCGCCA AGACATTATCGACTACGAAATTGTTCAGCACATCTTTGAGATTTTTCGTCTGACGGTC CAGATGCGCAACTCGCTGAGCGAGTTGGAAGATCGTGACTATGACCGTCTGATTAGC CCGGTGCTGAATGAAAACAATATCTTCTATGATAGCGCAAAGGCCGGTGACGCGCT GCCGAAAGATGCGGATGCTAACGGTGCATACTGCATTGCACTGAAGGGTCTGTACG AAATCAAACAGATCACCGAGAATTGGAAAGAGGATGGTAAGTTTAGCCGTGATAAG CTGAAGATTAGCAATAAAGACTGGTTCGACTTTATTCAAAACAAGCGCTATCTGAAA CGTCCGGCAGCGACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTA GCGGCGCAGGCAGCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACG TAAGGTTATTCCGGGCTAA SEQ ID NO: 44 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA CAACGGAACAAATAATTTTCAGAACTTTATTGGGATCAGTTCGCTTCAGAAAACGCT TCGTAATGCTCTGATTCCCACAGAAACCACTCAGCAGTTTATCGTAAAGAATGGCAT TATCAAGGAGGATGAATTACGCGGCGAGAACCGCCAAATCTTAAAAGATATCATGG ACGACTACTACCGCGGTTTCATTAGCGAAACTCTTAGTTCAATTGACGACATTGACT GGACGTCCTTGTTCGAAAAGATGGAGATTCAATTAAAGAACGGTGATAACAAGGAT ACGTTGATTAAAGAACAGACGGAGTACCGTAAGGCTATCCACAAAAAATTTGCAAA CGACGACCGCTTTAAAAATATGTTTAGCGCAAAATTAATCTCCGACATCCTGCCTGA ATTCGTCATCCATAACAATAACTATAGCGCCTCGGAAAAAGAAGAAAAAACGCAGG TTATTAAACTTTTCTCGCGCTTTGCAACAAGCTTTAAGGATTACTTCAAAAATCGCGC CAATTGTTTTTCAGCCGACGACATTAGCTCCAGTTCCTGCCACCGTATTGTGAATGAC AACGCTGAGATTTTTTTTTCCAATGCGCTGGTTTATCGTCGTATTGTTAAGAGCCTTA GTAACGACGACATTAATAAAATTAGCGGTGATATGAAGGATAGCTTGAAAGAAATG AGTCTGGAAGAGATCTATAGTTACGAGAAGTACGGCGAATTTATTACCCAGGAGGG CATTTCATTTTACAATGATATCTGTGGAAAAGTCAACTCCTTTATGAACTTGTATTGC CAAAAGAATAAAGAAAACAAAAACCTGTACAAACTGCAAAAGTTACACAAGCAGA TTTTGTGTATCGCAGACACGTCATACGAAGTACCGTACAAGTTTGAGTCCGATGAAG AAGTGTACCAAAGCGTTAATGGCTTTTTGGATAACATTTCGAGCAAACATATCGTAG AGCGTTTGCGTAAGATTGGTGATAATTACAACGGTTACAATTTAGACAAAATCTATA TCGTCTCTAAGTTTTACGAAAGTGTTTCTCAGAAAACTTACCGCGATTGGGAGACGA TCAACACTGCGCTGGAGATTCATTACAATAATATCCTTCCAGGTAACGGTAAAAGCA AAGCTGATAAGGTGAAAAAGGCGGTTAAAAATGACCTTCAAAAGTCTATCACAGAA ATCAACGAATTGGTCAGCAATTATAAGCTTTGCAGTGACGATAACATTAAGGCCGA GACTTACATCCATGAGATCTCTCACATTCTTAATAATTTTGAAGCGCAAGAGCTGAA ATACAATCCTGAAATCCATCTGGTCGAAAGTGAATTAAAAGCCTCCGAATTAAAAA ATGTCTTGGACGTGATCATGAATGCGTTCCATTGGTGCTCAGTTTTTATGACGGAAG AGTTGGTGGACAAAGACAACAATTTTTACGCCGAGCTTGAGGAAATTTACGACGAA ATTTACCCCGTTATTTCGTTATACAACCTTGTGCGTAATTACGTTACACAAAAGCCCT ATTCGACAAAGAAAATCAAGTTAAATTTCGGGATTCCCACATTAGCTGATGGATGGT CCAAATCCAAAGAATACTCGAATAACGCTATCATCCTTATGCGTGATAATTTGTACT ACTTAGGCATCTTCAATGCGAAGAACAAACCTGACAAGAAAATTATCGAAGGAAAC ACTTCGGAGAACAAAGGTGATTATAAAAAGATGATCTACAACTTGCTTCCCGGGCC AAACAAAATGATTCCCAAGGTATTTTTGAGTTCTAAAACCGGTGTCGAAACTTACAA ACCAAGTGCTTATATTTTGGAAGGATACAAACAGAACAAACATATCAAGTCTTCGA AAGACTTCGATATTACGTTCTGCCACGATCTGATCGATTACTTCAAGAACTGTATTG CTATTCACCCCGAGTGGAAGAACTTTGGATTTGATTTCTCCGACACGTCCACTTATG AAGATATCTCTGGCTTCTATCGCGAGGTTGAATTACAAGGGTATAAGATTGACTGGA CTTATATTTCGGAGAAGGATATCGATCTTTTGCAAGAAAAAGGGCAACTTTATTTAT TTCAGATCTATAACAAGGACTTTTCAAAAAAGAGCACTGGAAATGACAATCTGCAT ACCATGTACCTTAAGAACCTGTTCTCGGAAGAGAACCTGAAGGACATTGTACTTAAA CTGAATGGAGAGGCAGAGATCTTCTTTCGCAAATCAAGCATTAAGAACCCAATTATT CACAAAAAGGGGAGTATCTTAGTAAATCGCACATATGAGGCTGAGGAAAAAGATCA GTTTGGTAACATTCAGATCGTGCGTAAGAACATTCCTGAAAATATCTATCAGGAACT TTATAAGTATTTCAACGATAAAAGTGATAAAGAGCTGAGTGACGAAGCGGCTAAAC TTAAGAATGTTGTGGGACACCATGAGGCAGCAACCAATATTGTGAAGGATTATCGCT ATACGTACGACAAATACTTTTTACACATGCCCATCACTATTAATTTTAAAGCTAATA AGACTGGCTTCATTAACGATCGCATCCTGCAGTACATTGCTAAGGAAAAGGATCTTC ACGTTATCGGTATCGATCGCGGGGAGCGTAATCTTATCTACGTCTCTGTCATTGACA CGTGTGGCAATATTGTGGAGCAAAAGTCCTTCAATATTGTTAACGGCTATGACTATC AGATTAAATTGAAACAGCAGGAAGGTGCGCGTCAGATTGCCCGCAAGGAATGGAAG GAAATTGGCAAGATCAAAGAAATTAAGGAGGGCTACTTAAGCTTAGTAATTCACGA AATTAGTAAAATGGTTATCAAATACAACGCCATCATCGCGATGGAGGATCTTTCGTA CGGGTTTAAGAAAGGTCGTTTTAAAGTGGAGCGTCAGGTGTACCAGAAATTTGAAA CTATGCTTATTAACAAACTTAACTACCTGGTTTTCAAGGATATCAGTATTACTGAAA ACGGGGGGCTGTTAAAAGGGTATCAATTAACTTACATTCCAGACAAATTAAAGAAC GTTGGACATCAGTGTGGCTGCATTTTTTATGTACCAGCTGCATACACTTCAAAGATC GATCCTACGACTGGGTTCGTGAACATTTTTAAGTTTAAAGACTTGACGGTAGATGCC AAGCGCGAATTCATCAAGAAATTCGACAGCATTCGCTACGACTCTGAGAAAAATCTT TTCTGTTTCACATTCGATTATAACAATTTCATTACGCAGAACACAGTAATGTCCAAGT CTTCTTGGAGTGTTTATACATATGGTGTCCGCATTAAGCGCCGTTTCGTCAACGGCCG CTTCAGTAATGAGAGCGATACTATTGACATCACAAAAGACATGGAAAAAACACTGG AAATGACCGACATCAATTGGCGTGACGGCCATGACTTACGTCAGGATATCATTGATT ATGAGATCGTTCAACACATCTTCGAAATCTTTCGCTTGACTGTTCAAATGCGCAATTC CTTGTCGGAATTGGAGGACCGTGATTATGACCGCTTAATTTCCCCCGTCTTAAATGA AAACAATATTTTTTATGACTCTGCAAAAGCTGGAGATGCTCTGCCGAAAGACGCCGA TGCAAATGGGGCATATTGCATTGCTTTAAAGGGGCTTTACGAGATCAAGCAAATCAC CGAAAACTGGAAAGAGGATGGAAAGTTTTCGCGTGATAAACTGAAGATCTCTAACA AAGACTGGTTCGACTTTATCCAGAACAAGCGTTATTTGAAACGTCCGGCAGCGACCA AAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCC GAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCT AA SEQ ID NO: 45 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA CAACGGCACCAATAACTTCCAAAACTTCATCGGGATCTCTAGCCTTCAGAAGACGCT TCGCAATGCTCTTATCCCAACTGAGACCACTCAACAATTTATTGTGAAGAATGGAAT TATTAAAGAGGACGAACTGCGTGGCGAGAATCGTCAGATCTTAAAGGACATTATGG ATGATTATTACCGTGGATTCATCTCCGAAACATTATCGTCGATCGATGATATCGATT GGACTTCTCTGTTCGAGAAAATGGAAATTCAATTGAAAAACGGAGATAATAAAGAT ACGCTTATCAAAGAACAGACGGAATATCGTAAAGCGATTCATAAGAAATTCGCAAA TGACGATCGTTTCAAAAATATGTTCAGTGCCAAGCTTATTTCGGACATTTTACCTGA ATTTGTAATTCATAATAATAACTACTCAGCAAGTGAGAAGGAGGAGAAAACCCAAG TTATTAAACTGTTCTCTCGTTTCGCAACGTCCTTTAAAGATTACTTTAAAAACCGCGC GAATTGCTTTAGCGCTGACGACATTTCCAGCTCATCCTGTCATCGCATCGTAAACGA CAATGCGGAAATCTTCTTCAGCAACGCCCTGGTTTACCGCCGCATCGTCAAAAGCTT ATCGAATGACGACATCAATAAGATCTCAGGAGATATGAAGGACTCGCTTAAGGAGA TGTCTCTGGAGGAAATTTATAGTTACGAAAAGTATGGAGAGTTCATTACCCAGGAGG GAATCTCGTTCTACAATGACATTTGCGGGAAGGTGAACTCCTTCATGAACTTATACT GCCAGAAAAACAAAGAGAACAAAAATCTGTATAAATTGCAGAAATTACATAAACAG ATTCTTTGTATTGCTGACACTTCCTACGAAGTACCCTATAAATTCGAGTCAGATGAA GAAGTATACCAGTCCGTGAACGGATTTCTGGACAATATCTCCTCAAAACACATCGTG GAACGCTTACGTAAAATTGGCGATAATTATAATGGTTACAATCTTGACAAAATTTAT ATCGTATCTAAATTTTACGAGAGTGTGAGCCAAAAGACCTACCGCGACTGGGAGAC CATCAACACAGCTTTAGAAATTCACTATAATAATATCTTACCCGGCAATGGTAAGAG CAAGGCTGACAAGGTAAAAAAGGCCGTCAAGAATGATTTGCAGAAATCTATTACAG AAATTAATGAGTTAGTCTCCAACTATAAGCTTTGTTCCGACGATAACATCAAAGCTG AGACATATATTCATGAGATTAGTCACATTCTTAACAACTTCGAGGCCCAGGAACTTA AGTACAATCCTGAAATTCATCTTGTCGAGTCTGAGCTGAAAGCTAGTGAATTGAAAA ATGTTTTAGACGTTATTATGAACGCATTCCACTGGTGCTCTGTGTTTATGACAGAAG AACTGGTCGACAAGGACAATAACTTCTATGCCGAACTTGAGGAAATCTACGATGAA ATTTACCCTGTAATCTCCTTGTATAATCTTGTACGTAATTACGTCACTCAAAAACCTT ACAGCACGAAAAAAATTAAATTGAACTTCGGGATTCCTACACTTGCCGACGGGTGG TCTAAATCCAAGGAATATAGCAACAATGCCATTATTTTAATGCGCGACAATCTTTAC TATTTAGGAATTTTTAACGCTAAGAACAAGCCCGATAAAAAGATTATTGAAGGAAA CACGTCTGAAAATAAGGGCGACTACAAAAAGATGATTTATAACCTTTTGCCCGGTCC AAACAAAATGATCCCAAAGGTATTCCTGTCATCCAAAACAGGGGTTGAGACATATA AGCCCAGCGCATATATTCTGGAAGGATACAAACAGAATAAACATATCAAAAGCAGC AAAGATTTTGACATTACTTTTTGCCACGATTTAATCGACTACTTCAAAAACTGTATCG CTATCCACCCTGAATGGAAGAATTTCGGATTTGATTTCTCAGATACAAGTACGTATG AGGATATCAGCGGTTTCTATCGCGAAGTTGAACTTCAAGGGTATAAAATTGACTGGA CCTACATTAGTGAGAAGGACATCGACCTGTTACAGGAAAAAGGCCAATTGTACTTGT TTCAGATCTACAATAAGGATTTCTCAAAAAAATCGACCGGCAATGATAACTTGCACA CCATGTACCTGAAGAACCTTTTTTCGGAGGAAAACCTTAAAGACATTGTCCTGAAGT TGAATGGAGAAGCGGAGATTTTCTTTCGTAAGTCTTCCATTAAAAATCCAATTATTC ATAAGAAGGGCAGCATCCTTGTGAACCGTACGTACGAGGCGGAAGAGAAGGACCA ATTCGGTAACATTCAAATCGTCCGCAAGAACATCCCTGAAAATATTTATCAGGAGCT TTACAAGTATTTCAATGATAAGTCCGACAAGGAATTATCAGATGAGGCTGCGAAGTT GAAAAATGTTGTTGGTCATCACGAGGCGGCGACGAATATTGTAAAGGATTATCGCT ACACTTATGACAAGTACTTTCTGCACATGCCGATCACCATTAATTTCAAGGCGAACA AAACAGGATTTATTAATGACCGCATCTTACAATACATTGCCAAAGAAAAGGACTTAC ACGTTATTGGCATTGATCGTGGAGAACGCAACTTAATCTACGTAAGCGTTATTGACA CTTGCGGGAATATCGTAGAACAAAAGAGCTTCAACATCGTGAATGGTTACGATTACC AGATCAAGCTTAAGCAGCAGGAGGGAGCGCGCCAGATCGCGCGCAAGGAATGGAA GGAGATTGGTAAGATCAAGGAAATCAAGGAAGGTTATCTGTCCTTGGTAATCCACG AAATTTCGAAAATGGTTATCAAATACAATGCTATTATTGCAATGGAGGACTTGTCCT ACGGCTTTAAAAAAGGACGCTTTAAGGTGGAGCGCCAGGTTTATCAAAAGTTTGAA ACAATGCTGATTAACAAGCTGAACTATTTGGTCTTTAAAGATATCTCCATCACCGAA AATGGTGGGCTTTTGAAAGGCTATCAACTTACATATATCCCTGATAAGCTTAAGAAT GTGGGTCATCAGTGCGGGTGCATTTTTTATGTTCCTGCAGCCTACACGTCCAAAATC GATCCTACAACTGGATTTGTTAATATCTTCAAATTTAAGGATCTTACCGTCGACGCG AAGCGCGAATTTATCAAGAAATTCGATAGTATTCGTTATGATTCCGAAAAAAACCTT TTCTGTTTCACCTTTGATTATAATAACTTTATCACGCAAAATACTGTCATGAGCAAAT CGAGTTGGTCTGTGTACACTTACGGAGTACGCATCAAGCGTCGTTTTGTTAATGGGC GCTTCAGTAACGAGTCAGACACGATTGATATCACAAAAGATATGGAGAAAACGCTG GAGATGACAGACATCAATTGGCGCGATGGTCATGACTTACGTCAAGACATTATCGAT TATGAAATTGTCCAGCATATCTTTGAGATCTTTCGTTTGACTGTTCAGATGCGCAACA GCCTGTCAGAATTGGAGGATCGTGACTATGATCGCCTTATTTCTCCCGTCTTAAATG AGAACAATATCTTCTACGACTCAGCCAAGGCTGGAGATGCACTGCCAAAAGACGCC GACGCAAATGGGGCCTACTGTATTGCATTGAAGGGGTTGTACGAGATCAAACAGAT TACAGAAAATTGGAAGGAGGACGGTAAGTTCTCTCGTGATAAGCTGAAGATTTCTA ACAAAGACTGGTTCGATTTCATTCAGAACAAACGTTACCTGAAACGTCCGGCAGCG ACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCA GCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCG GGCTAA SEQ ID NO: 46 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA CAACGGTACCAATAACTTTCAGAATTTCATTGGAATCAGCAGCTTACAGAAAACCCT GCGCAATGCACTTATCCCCACTGAGACAACCCAGCAGTTCATTGTAAAGAACGGGA TTATTAAAGAAGATGAGCTTCGCGGGGAGAATCGTCAGATCTTAAAGGATATTATG GACGATTACTACCGTGGCTTCATTTCGGAGACGCTGTCGTCGATCGACGACATCGAC TGGACATCCTTGTTTGAAAAGATGGAAATCCAACTGAAGAATGGCGATAACAAGGA CACGTTAATCAAAGAGCAGACGGAATACCGTAAAGCTATCCACAAAAAGTTCGCTA ATGACGACCGCTTTAAGAACATGTTCTCAGCAAAACTTATTAGCGATATTTTACCTG AATTTGTCATCCACAATAACAATTACTCCGCGAGTGAAAAAGAGGAGAAAACCCAG GTGATTAAGCTGTTTTCCCGTTTTGCAACCAGTTTCAAGGACTATTTTAAGAATCGTG CTAATTGTTTCTCTGCAGACGACATTTCCTCGTCGTCCTGCCATCGCATTGTTAATGA TAATGCTGAAATCTTTTTTTCAAACGCACTTGTGTATCGTCGCATTGTCAAAAGCTTA AGTAATGACGATATCAATAAGATCTCAGGAGACATGAAGGACTCCCTGAAAGAAAT GTCATTGGAAGAAATTTACTCTTATGAAAAGTATGGAGAATTTATTACGCAGGAGGG TATCAGCTTCTATAACGACATTTGTGGTAAAGTGAACAGCTTTATGAATCTTTATTGT CAAAAGAATAAAGAGAACAAAAATCTGTACAAGCTGCAGAAATTGCATAAACAAAT TCTGTGCATTGCAGATACTTCGTATGAGGTTCCTTACAAATTCGAGTCGGATGAGGA GGTGTATCAAAGCGTAAACGGATTTTTGGATAACATTAGTAGTAAGCATATTGTGGA ACGCCTTCGCAAGATTGGTGACAACTATAACGGATACAACTTAGACAAGATCTATAT TGTCTCGAAGTTTTACGAAAGTGTTTCCCAAAAGACTTATCGCGACTGGGAGACAAT CAACACTGCGCTGGAAATTCACTATAACAATATCTTGCCGGGGAACGGAAAAAGTA AGGCAGATAAGGTGAAGAAAGCAGTCAAAAATGATCTGCAAAAAAGCATTACTGA AATTAACGAACTTGTGTCAAATTACAAATTGTGTTCGGATGACAATATTAAAGCGGA AACGTATATCCACGAGATCTCGCACATTCTTAATAATTTCGAGGCGCAGGAATTAAA GTATAATCCTGAGATCCATTTGGTGGAATCAGAACTTAAAGCTAGTGAACTGAAAA ATGTCCTGGACGTTATTATGAATGCATTTCACTGGTGTTCTGTCTTTATGACAGAAGA ACTTGTCGACAAAGACAACAACTTTTATGCGGAATTAGAAGAGATTTACGACGAAA TTTATCCCGTTATTTCGTTATATAATTTAGTTCGTAATTACGTGACTCAGAAACCCTA CAGCACAAAAAAGATTAAATTAAACTTTGGGATTCCGACTCTTGCTGATGGATGGAG CAAGTCCAAGGAGTACTCTAATAACGCCATTATCTTGATGCGTGACAACCTGTACTA CCTGGGCATTTTTAACGCTAAAAACAAACCCGACAAAAAGATCATTGAAGGGAACA CCTCGGAAAATAAGGGGGACTATAAAAAAATGATCTACAATCTGTTGCCAGGCCCA AATAAGATGATCCCAAAGGTTTTTTTATCTTCCAAAACTGGCGTAGAAACTTACAAG CCGAGCGCATACATCCTTGAAGGATATAAACAAAACAAACATATCAAAAGTTCAAA GGACTTCGATATTACGTTCTGCCATGATTTAATCGATTATTTCAAGAATTGCATCGCG ATTCACCCAGAGTGGAAAAACTTTGGGTTTGATTTTTCAGACACCAGCACTTACGAG GATATTAGTGGATTCTATCGTGAGGTTGAACTGCAGGGCTATAAAATTGACTGGACC TATATTTCTGAAAAAGATATTGATCTGCTTCAGGAGAAAGGCCAATTGTACTTATTT CAAATCTATAACAAGGATTTCTCCAAGAAGTCCACGGGTAATGACAACTTACACAC AATGTATCTGAAGAATCTGTTTAGTGAGGAGAACTTGAAGGACATTGTGCTGAAGCT TAATGGCGAGGCCGAAATCTTTTTTCGTAAGTCCTCCATTAAAAACCCTATTATCCAT AAGAAAGGGAGTATTCTTGTCAACCGCACGTATGAGGCCGAAGAAAAGGACCAATT CGGAAACATCCAAATTGTCCGTAAAAATATTCCTGAGAACATTTACCAGGAGCTTTA CAAGTATTTCAACGACAAGAGTGATAAAGAACTTTCAGATGAGGCGGCGAAACTGA AGAATGTAGTGGGGCACCACGAAGCTGCCACGAATATTGTAAAGGATTACCGTTAC ACCTACGACAAGTACTTTTTGCATATGCCCATCACAATTAATTTTAAGGCCAATAAA ACTGGTTTTATCAACGATCGTATCTTACAGTACATTGCTAAGGAAAAAGATCTGCAC GTTATCGGTATCGATCGCGGGGAACGCAATCTGATTTATGTTAGTGTGATTGACACG TGCGGAAATATTGTTGAGCAGAAGAGCTTTAATATCGTAAATGGATATGACTATCAA ATTAAACTGAAGCAACAGGAAGGGGCCCGCCAGATTGCCCGCAAGGAGTGGAAAG AAATTGGAAAGATCAAGGAGATTAAAGAAGGGTACCTTTCCCTTGTTATCCACGAA ATCTCGAAAATGGTGATCAAGTACAATGCCATTATTGCTATGGAGGATCTGTCATAT GGGTTTAAGAAAGGCCGCTTTAAGGTGGAACGTCAGGTTTACCAGAAGTTTGAGAC CATGCTTATCAATAAGCTGAATTATCTTGTCTTCAAAGACATCTCAATCACAGAGAA CGGCGGGCTGTTAAAAGGATATCAGCTGACCTATATCCCCGACAAACTGAAAAATG TCGGGCACCAATGCGGCTGTATTTTCTACGTGCCCGCTGCATACACATCTAAAATTG ACCCAACGACTGGATTCGTAAATATTTTTAAGTTTAAGGATCTTACGGTAGATGCAA AGCGCGAATTTATCAAGAAATTTGATAGTATCCGTTACGACAGCGAGAAAAACTTAT TTTGTTTTACGTTCGATTATAACAACTTCATCACGCAAAATACCGTCATGTCAAAATC TTCCTGGTCAGTCTATACGTATGGCGTCCGTATCAAGCGCCGCTTCGTCAACGGGCG TTTTTCAAACGAGTCAGATACCATCGATATCACCAAAGATATGGAAAAAACATTGG AGATGACGGACATCAATTGGCGCGATGGTCATGACTTACGCCAGGACATTATTGACT ACGAAATCGTACAACATATTTTTGAGATTTTCCGTCTGACCGTGCAAATGCGCAACT CATTATCCGAACTTGAGGATCGTGATTACGACCGCTTGATCAGTCCTGTTCTGAACG AGAATAATATTTTTTACGACAGTGCCAAGGCGGGAGACGCACTGCCCAAGGACGCT GACGCTAACGGAGCTTATTGTATTGCGTTGAAGGGACTTTACGAAATCAAGCAAATC ACTGAAAACTGGAAGGAGGATGGTAAATTCTCACGCGACAAGTTGAAAATTTCGAA CAAGGACTGGTTCGATTTCATCCAAAACAAGCGTTATTTAAAACGTCCGGCAGCGAC CAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGC CCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGG GCTAA SEQ ID NO: 47 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA CAACGGGACTAATAACTTCCAGAACTTCATCGGTATTTCATCATTACAAAAAACGCT TCGTAACGCCTTGATCCCAACAGAAACGACCCAACAATTTATTGTAAAAAACGGCAT CATCAAAGAAGACGAACTGCGTGGCGAAAATCGCCAAATTTTGAAGGACATTATGG ATGACTATTATCGTGGGTTTATCTCGGAGACATTATCCTCCATCGACGACATTGATTG GACGAGTCTTTTTGAGAAAATGGAGATCCAGCTTAAAAATGGTGATAACAAGGATA CATTGATCAAGGAGCAAACCGAGTACCGCAAGGCCATCCATAAGAAGTTCGCAAAT GACGACCGCTTCAAAAATATGTTTAGTGCCAAATTGATCTCGGATATCCTTCCTGAG TTCGTAATTCACAACAATAATTATAGCGCATCCGAAAAGGAGGAAAAGACTCAAGT CATTAAGCTTTTCAGTCGCTTTGCTACCTCGTTTAAGGACTATTTCAAGAACCGCGCG AACTGCTTCTCAGCGGATGACATTTCTTCCTCGTCGTGTCACCGCATCGTGAATGATA ATGCGGAGATCTTCTTTAGTAATGCCTTGGTATACCGCCGCATTGTTAAATCCCTGTC TAACGACGATATCAATAAGATCTCAGGAGATATGAAGGATAGCCTTAAAGAAATGT CTCTGGAAGAAATTTACTCCTATGAAAAGTACGGTGAGTTTATCACCCAAGAGGGG ATTAGCTTTTATAACGATATCTGCGGGAAGGTGAATTCGTTTATGAACCTTTATTGTC AAAAGAATAAGGAGAATAAGAACTTATATAAGCTTCAGAAACTGCATAAACAAATC TTATGCATTGCCGATACTAGCTATGAAGTTCCGTATAAATTCGAGAGCGATGAAGAA GTTTATCAGAGCGTCAATGGGTTCTTGGATAACATTTCATCAAAACACATCGTGGAA CGTCTGCGTAAGATTGGGGATAACTACAACGGATATAATCTTGACAAAATTTATATT GTATCTAAATTCTATGAGTCGGTGAGTCAAAAGACCTACCGTGATTGGGAAACAATC AATACCGCGTTAGAAATCCACTATAACAACATTCTGCCAGGGAATGGTAAAAGTAA AGCGGACAAAGTCAAGAAGGCTGTGAAGAACGATCTGCAAAAGAGTATTACAGAG ATTAACGAATTAGTCTCCAATTATAAGTTATGCTCGGACGATAACATTAAGGCGGAG ACGTATATTCATGAGATTTCGCATATTCTTAACAACTTCGAGGCACAAGAGCTTAAG TATAACCCAGAGATTCACCTTGTCGAATCGGAGCTGAAGGCATCGGAATTAAAAAA TGTCTTAGATGTAATCATGAACGCGTTCCATTGGTGCAGTGTTTTCATGACTGAGGA GTTAGTTGACAAGGACAATAACTTCTACGCAGAATTAGAAGAGATCTATGATGAGA TTTATCCAGTGATTTCGCTGTATAATCTGGTACGTAATTACGTCACTCAAAAGCCCTA CTCAACAAAAAAAATTAAGCTGAACTTCGGAATTCCGACTCTGGCCGACGGGTGGT CCAAGTCAAAGGAGTATTCTAATAATGCTATCATCCTGATGCGCGATAACTTATACT ATTTGGGAATTTTCAATGCCAAAAATAAACCAGATAAAAAGATTATCGAAGGTAAT ACAAGCGAGAATAAGGGTGACTATAAGAAAATGATTTACAATCTTCTTCCAGGCCCT AACAAGATGATTCCCAAAGTTTTTTTGTCCAGTAAAACAGGGGTCGAAACTTACAAG CCCAGTGCCTATATCCTTGAAGGGTACAAGCAGAATAAGCACATCAAATCCTCGAA AGACTTTGATATTACATTTTGTCATGACTTAATCGATTATTTTAAGAACTGTATCGCA ATCCATCCAGAATGGAAGAACTTCGGGTTTGATTTCTCTGATACTTCCACGTATGAG GATATTTCCGGGTTCTACCGCGAAGTAGAGCTTCAGGGCTATAAAATTGACTGGACA TATATTTCAGAAAAAGACATCGATCTGTTACAAGAAAAAGGACAGTTGTATCTGTTT CAAATCTATAATAAGGATTTCTCCAAAAAGTCAACTGGAAATGATAACTTACATACA ATGTATCTGAAAAATCTTTTTAGTGAAGAGAATTTGAAGGATATCGTGCTGAAGTTA AATGGCGAAGCAGAGATCTTCTTCCGCAAGTCCTCGATCAAGAATCCTATCATCCAC AAGAAAGGTAGTATTCTGGTTAACCGCACGTACGAGGCCGAGGAAAAAGACCAGTT CGGTAATATCCAGATTGTACGTAAGAATATTCCTGAAAATATTTACCAGGAATTATA CAAGTATTTTAACGACAAATCGGATAAGGAGCTTTCAGATGAGGCCGCAAAGTTGA AGAACGTCGTAGGACACCATGAGGCCGCTACGAATATCGTCAAGGACTACCGCTAT ACGTATGACAAGTACTTCCTGCACATGCCTATTACTATCAATTTCAAAGCTAATAAA ACAGGATTCATCAATGATCGTATCCTTCAGTACATTGCCAAAGAAAAAGATCTGCAC GTAATCGGAATCGACCGTGGCGAACGTAATCTGATTTACGTATCAGTTATCGACACA TGTGGTAACATCGTGGAGCAGAAATCTTTTAACATTGTTAACGGCTATGATTATCAG ATTAAGCTTAAACAGCAGGAGGGGGCACGCCAAATCGCTCGTAAAGAATGGAAGGA GATTGGAAAGATTAAAGAGATTAAAGAGGGGTACCTTTCGCTGGTTATTCACGAAA TTTCCAAGATGGTGATTAAGTACAATGCAATCATCGCGATGGAAGATCTTAGTTACG GATTCAAAAAGGGACGCTTCAAAGTTGAGCGTCAGGTCTACCAGAAATTTGAAACG ATGCTGATTAACAAATTGAATTACTTGGTATTCAAAGATATCTCAATTACTGAAAAT GGTGGCTTATTAAAGGGTTACCAGCTTACCTATATCCCGGATAAGCTGAAGAACGTG GGCCATCAATGCGGCTGCATCTTTTACGTCCCTGCCGCATATACCTCTAAAATTGAC CCCACCACCGGATTCGTAAATATTTTTAAATTCAAGGACCTGACGGTGGACGCCAAG CGCGAATTCATCAAAAAATTCGACTCAATCCGCTATGATTCCGAAAAAAATCTTTTC TGCTTTACGTTCGATTATAATAACTTCATTACCCAAAACACGGTGATGTCAAAATCG TCCTGGAGCGTGTATACTTATGGAGTGCGTATCAAGCGCCGCTTTGTTAATGGGCGC TTCAGTAACGAAAGCGATACCATCGACATTACCAAAGACATGGAGAAGACGCTTGA AATGACGGATATCAATTGGCGTGACGGACACGATCTTCGTCAGGATATCATCGACTA CGAGATTGTGCAACATATCTTTGAGATTTTCCGTTTAACTGTTCAAATGCGTAACTCC TTGTCCGAATTGGAAGACCGTGATTACGACCGCTTGATTTCACCAGTGCTTAACGAG AATAACATCTTCTACGACTCCGCCAAAGCAGGCGATGCCCTGCCAAAGGACGCTGA TGCAAATGGTGCATACTGTATCGCGTTGAAGGGCTTATACGAGATTAAGCAAATCAC CGAAAATTGGAAAGAGGATGGAAAGTTCAGTCGCGATAAGCTGAAGATCTCTAATA AAGATTGGTTTGACTTTATCCAGAACAAACGTTATTTAAAACGTCCGGCAGCGACCA AAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCC GAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCT AA SEQ ID NO: 48 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA CAACGGTACCAATAATTTCCAAAATTTCATCGGAATCTCATCCTTGCAAAAAACCTT GCGCAATGCTTTGATCCCCACCGAAACCACGCAGCAGTTCATCGTGAAAAACGGCA TTATCAAAGAGGATGAGTTGCGCGGGGAAAACCGTCAAATTCTTAAGGATATCATG GACGATTACTACCGTGGGTTTATCAGTGAGACCCTGTCAAGCATTGACGACATTGAC TGGACCAGCTTATTTGAGAAGATGGAGATTCAATTAAAGAACGGGGACAATAAGGA CACGCTTATCAAAGAGCAGACAGAATACCGTAAAGCGATTCATAAGAAATTTGCAA ATGACGATCGCTTCAAGAACATGTTTTCAGCAAAATTAATCAGCGACATCCTTCCCG AATTTGTGATTCATAATAACAACTATTCGGCTAGCGAAAAAGAGGAGAAAACTCAG GTTATTAAGCTTTTCTCGCGTTTTGCCACTTCGTTCAAAGACTATTTTAAGAATCGCG CAAACTGCTTTTCGGCTGATGATATTTCCAGTTCTAGCTGCCATCGTATCGTTAACGA TAATGCTGAGATTTTCTTCTCTAATGCCCTGGTGTATCGTCGTATCGTTAAATCTTTG AGCAACGACGATATTAATAAGATTTCAGGCGACATGAAGGATTCTTTAAAGGAGAT GTCTTTAGAAGAGATTTATTCCTATGAGAAATATGGCGAGTTTATCACCCAAGAAGG AATTTCGTTCTACAACGACATCTGTGGCAAAGTGAACAGCTTCATGAATTTATACTG CCAAAAGAATAAGGAGAATAAAAATTTATATAAACTGCAGAAACTGCATAAGCAAA TTCTTTGCATTGCAGACACCTCTTATGAAGTTCCTTATAAGTTTGAATCGGACGAGG AGGTATATCAGAGTGTGAACGGGTTCCTGGACAATATTTCATCCAAGCATATTGTTG AACGTTTACGCAAAATTGGAGACAATTACAATGGGTATAACCTTGACAAAATTTACA TCGTGTCGAAGTTTTACGAATCGGTAAGCCAGAAGACCTATCGTGACTGGGAAACTA TCAATACCGCCTTAGAAATTCATTACAACAATATTCTTCCTGGTAACGGCAAAAGCA AAGCCGATAAGGTAAAGAAGGCTGTCAAGAACGACCTGCAAAAGTCTATCACAGAG ATCAACGAGTTAGTCTCTAACTACAAATTATGTTCCGACGACAATATTAAAGCCGAA ACCTACATCCATGAGATCTCACACATTCTTAACAATTTTGAGGCCCAGGAGCTGAAA TATAACCCAGAAATTCACCTTGTAGAGAGCGAATTAAAAGCCTCCGAGCTGAAGAA CGTTTTGGATGTAATCATGAACGCATTTCATTGGTGCAGCGTATTTATGACAGAGGA GTTGGTCGACAAGGACAATAACTTTTACGCCGAGCTTGAAGAAATCTACGATGAAA TTTACCCGGTAATTAGTTTATATAATTTAGTTCGCAACTACGTAACTCAGAAACCCTA CAGTACCAAGAAGATTAAATTGAACTTTGGGATCCCGACACTTGCTGACGGTTGGAG TAAATCAAAAGAATACTCCAATAATGCAATTATCCTGATGCGCGACAATCTTTACTA CTTGGGGATCTTTAACGCAAAGAACAAACCAGATAAGAAAATCATCGAGGGCAACA CCAGCGAGAATAAAGGCGATTACAAGAAAATGATCTATAATCTTTTGCCGGGACCG AACAAAATGATCCCAAAGGTTTTCCTGTCGTCGAAAACGGGAGTCGAGACATATAA ACCATCTGCGTACATCTTGGAAGGTTACAAACAGAATAAGCATATTAAGTCTAGTAA AGACTTCGACATCACCTTTTGTCATGACCTGATTGATTATTTCAAGAACTGTATTGCT ATCCATCCAGAATGGAAAAACTTCGGATTTGACTTCTCCGATACTAGCACCTACGAA GACATTTCGGGTTTTTATCGCGAAGTAGAGCTTCAAGGGTACAAAATTGATTGGACA TATATTAGCGAGAAAGACATTGATTTGCTTCAAGAGAAGGGACAGTTATATTTATTC CAGATCTACAACAAAGACTTCTCGAAGAAATCCACCGGTAATGATAATCTTCACACT ATGTACCTGAAGAATTTATTTTCAGAGGAAAATCTGAAGGACATTGTACTTAAACTT AATGGAGAAGCCGAAATCTTCTTCCGCAAGAGTTCCATTAAAAATCCGATTATTCAT AAAAAGGGAAGTATCCTTGTGAACCGCACGTATGAGGCCGAAGAGAAGGATCAGTT TGGGAATATTCAAATTGTCCGCAAAAACATCCCCGAGAACATCTACCAGGAACTGT ATAAATACTTTAATGATAAATCTGATAAAGAGTTATCAGACGAGGCTGCCAAACTG AAAAACGTAGTCGGTCATCATGAGGCAGCGACCAATATTGTAAAGGACTACCGTTA CACCTACGACAAGTATTTCCTTCACATGCCGATCACGATTAATTTTAAGGCTAACAA GACCGGCTTTATCAATGACCGCATCTTGCAGTACATCGCGAAAGAGAAAGATTTACA CGTCATCGGAATTGATCGTGGAGAGCGTAATCTTATCTACGTCAGCGTCATCGACAC CTGTGGAAACATTGTGGAACAAAAAAGTTTTAATATCGTAAACGGCTACGACTATCA AATTAAACTTAAACAGCAAGAGGGAGCTCGCCAGATCGCTCGCAAAGAGTGGAAAG AGATTGGGAAAATTAAAGAAATTAAAGAGGGTTACCTGTCGCTGGTAATTCACGAA ATCTCGAAAATGGTCATCAAATATAATGCAATTATCGCTATGGAGGATCTGTCCTAC GGGTTCAAGAAGGGACGTTTTAAAGTAGAGCGCCAGGTGTATCAAAAATTCGAAAC CATGTTGATCAATAAGCTTAACTATTTGGTCTTCAAAGATATTTCGATTACGGAGAA CGGAGGTTTGTTGAAAGGATATCAGCTGACGTATATCCCAGACAAGTTGAAAAACG TGGGGCATCAATGTGGATGTATTTTCTATGTGCCCGCGGCCTACACGAGTAAGATCG ATCCTACCACTGGTTTCGTCAACATTTTCAAATTTAAAGATCTTACCGTGGATGCGA AGCGCGAATTTATTAAGAAATTTGATAGCATTCGCTATGATTCCGAAAAGAACCTGT TCTGTTTTACGTTCGACTATAACAATTTCATTACCCAAAACACGGTGATGAGCAAAT CCTCTTGGTCAGTTTATACATACGGTGTACGTATCAAACGCCGTTTCGTTAACGGAC GCTTTTCCAATGAGTCTGATACAATCGATATCACGAAAGATATGGAAAAAACATTAG AGATGACTGATATCAACTGGCGTGACGGGCACGACCTGCGTCAAGACATTATTGACT ACGAGATTGTGCAGCATATCTTCGAAATCTTTCGCTTAACTGTGCAAATGCGTAACT CGTTATCCGAGTTAGAAGACCGTGACTACGATCGCCTGATTTCACCCGTCTTGAACG AAAATAACATCTTCTACGATTCCGCGAAGGCTGGGGACGCATTGCCCAAGGACGCA GACGCGAATGGAGCGTACTGTATTGCGCTTAAAGGATTATATGAAATCAAGCAGAT CACCGAAAATTGGAAGGAGGACGGGAAGTTCTCACGCGACAAACTGAAGATTTCAA ATAAGGACTGGTTCGATTTCATTCAGAATAAGCGTTACCTGAAACGTCCGGCAGCGA CCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAG CCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGG GCTAA SEQ ID NO: 49 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA TAATGGTACGAACAACTTTCAGAACTTCATCGGCATCTCCAGCCTTCAAAAGACTTT ACGCAACGCATTGATTCCCACGGAGACTACGCAACAGTTTATCGTAAAAAATGGTAT TATCAAAGAAGATGAATTACGCGGGGAGAATCGCCAGATTCTTAAGGACATTATGG ACGATTATTACCGTGGATTCATCAGTGAGACACTGAGCTCCATTGATGACATCGACT GGACGTCATTGTTTGAAAAGATGGAAATCCAGTTGAAAAATGGCGATAACAAAGAT ACATTGATTAAAGAGCAGACAGAGTACCGCAAAGCAATTCACAAGAAATTCGCCAA TGATGATCGTTTTAAGAACATGTTTAGTGCCAAGCTTATTTCGGATATCTTACCCGAA TTCGTGATTCACAACAACAATTATTCGGCAAGTGAGAAAGAGGAAAAGACCCAGGT TATCAAATTGTTTTCGCGCTTCGCCACTTCGTTCAAAGATTATTTCAAGAACCGTGCA AACTGTTTCTCCGCTGACGACATCAGTTCCAGCTCATGCCACCGTATTGTAAATGAC AATGCGGAGATCTTTTTCAGTAATGCCTTAGTATATCGTCGCATTGTAAAGAGCTTA TCTAATGATGACATTAACAAGATCTCGGGTGATATGAAGGACTCACTTAAGGAGAT GAGTCTGGAAGAGATCTACTCCTACGAAAAATACGGGGAATTCATCACCCAGGAGG GAATTTCATTCTACAACGATATCTGCGGCAAAGTTAACTCCTTTATGAATCTGTACTG TCAAAAGAACAAGGAGAATAAAAACCTGTATAAATTGCAGAAACTTCATAAACAAA TTTTGTGTATCGCAGACACGAGTTATGAAGTACCTTATAAATTCGAATCCGACGAAG AGGTATATCAGTCCGTAAATGGGTTCCTGGACAATATCAGTAGTAAGCACATTGTGG AACGCTTACGCAAAATTGGAGACAATTACAACGGGTATAACCTGGACAAAATCTAC ATCGTATCCAAATTTTATGAAAGCGTGTCTCAAAAAACTTATCGTGATTGGGAAACA ATCAACACGGCTCTTGAGATCCATTACAATAACATCTTGCCGGGTAACGGCAAATCG AAGGCAGACAAAGTTAAAAAAGCAGTTAAGAACGACTTACAGAAAAGCATTACGG AGATTAACGAGTTAGTAAGTAATTACAAATTATGCTCCGACGATAATATCAAAGCTG AAACCTACATCCATGAAATTAGCCACATTTTGAACAATTTCGAAGCGCAGGAGCTGA AATATAACCCTGAAATCCATCTGGTAGAGTCTGAGTTGAAGGCGTCAGAACTGAAA AACGTTCTTGACGTCATCATGAATGCCTTTCACTGGTGTAGTGTTTTTATGACTGAGG AGCTTGTAGATAAGGACAACAACTTCTATGCTGAACTTGAAGAGATCTACGATGAA ATCTACCCCGTAATCAGTCTGTATAATTTAGTTCGTAACTACGTCACGCAGAAACCC TATTCGACTAAGAAAATTAAGCTGAACTTTGGGATCCCTACTTTGGCAGACGGGTGG AGCAAGAGTAAAGAATACAGTAATAATGCAATTATCTTGATGCGCGATAACTTATAT TACTTAGGTATTTTCAATGCTAAGAACAAACCTGATAAGAAGATTATCGAAGGAAAT ACGAGTGAGAATAAGGGAGACTACAAAAAGATGATTTACAACTTGCTGCCAGGGCC TAATAAGATGATTCCAAAAGTTTTTCTGTCGAGCAAGACAGGGGTTGAAACTTATAA GCCATCCGCTTATATCCTTGAGGGGTACAAGCAGAATAAGCATATCAAGTCCTCCAA AGATTTTGATATTACATTTTGCCACGACTTAATTGATTACTTCAAGAACTGCATCGCA ATCCATCCCGAATGGAAGAATTTCGGCTTCGATTTCTCAGATACGTCCACGTATGAG GATATCTCAGGCTTTTACCGCGAAGTTGAGCTGCAAGGTTATAAAATTGATTGGACA TACATCTCCGAAAAAGACATTGATCTTTTACAGGAAAAGGGCCAATTATACTTATTT CAAATCTATAACAAAGATTTTAGCAAGAAGTCCACAGGTAATGATAACCTGCATAC GATGTATTTGAAAAATCTTTTCAGTGAAGAGAATTTGAAGGATATCGTCCTGAAGCT GAACGGTGAGGCTGAGATCTTCTTCCGCAAATCGTCTATCAAAAACCCCATCATTCA CAAAAAGGGAAGTATCTTAGTAAACCGCACTTATGAAGCGGAGGAAAAGGATCAGT TCGGGAACATCCAGATCGTGCGCAAGAACATTCCAGAAAACATCTATCAGGAACTT TACAAATATTTCAATGACAAGTCTGATAAAGAATTATCAGACGAGGCGGCGAAACT TAAAAATGTTGTTGGACACCACGAAGCAGCGACGAATATTGTAAAGGATTATCGCT ACACATACGATAAATACTTTTTGCACATGCCAATCACCATTAACTTTAAGGCGAACA AGACAGGTTTCATTAACGACCGTATTCTGCAATATATCGCAAAGGAAAAAGACCTG CACGTTATTGGGATCGATCGTGGCGAACGCAATTTGATCTACGTAAGCGTTATCGAC ACTTGCGGAAATATCGTTGAACAAAAAAGCTTTAATATCGTCAATGGATACGATTAC CAAATCAAGCTGAAACAACAAGAAGGGGCACGTCAGATCGCTCGTAAAGAATGGA AAGAGATTGGTAAGATCAAAGAGATTAAAGAAGGGTATCTTTCTTTAGTAATTCACG AGATTTCGAAAATGGTTATTAAATACAATGCGATTATTGCTATGGAAGACTTAAGCT ACGGCTTTAAGAAAGGTCGCTTCAAAGTGGAGCGCCAAGTGTATCAGAAGTTTGAA ACGATGTTGATTAACAAATTAAATTACCTGGTCTTTAAGGACATCAGTATCACAGAA AATGGGGGGTTGCTTAAAGGGTACCAGCTTACATACATCCCTGATAAACTGAAAAA TGTCGGTCATCAGTGCGGATGTATCTTCTATGTACCAGCAGCCTATACCAGTAAGAT TGACCCTACTACTGGCTTTGTGAATATTTTTAAATTCAAGGATTTAACCGTGGACGCC AAGCGTGAATTTATTAAAAAATTTGATTCGATTCGCTACGACAGTGAGAAAAACCTT TTCTGCTTTACCTTTGACTACAACAATTTTATTACCCAGAACACCGTAATGTCAAAGA GTTCGTGGTCTGTATATACCTACGGTGTTCGCATCAAGCGCCGCTTCGTAAACGGGC GTTTCAGTAACGAATCTGACACCATCGACATCACTAAAGATATGGAGAAGACATTG GAAATGACGGACATTAATTGGCGTGATGGCCATGACTTACGTCAGGACATTATTGAT TACGAAATTGTGCAGCATATCTTCGAGATTTTCCGTTTGACAGTTCAGATGCGCAAC TCACTGAGTGAGTTAGAAGATCGCGATTACGACCGTCTGATCTCACCGGTCCTTAAT GAAAACAACATTTTCTACGACTCAGCAAAGGCGGGTGATGCCCTGCCAAAGGATGC GGACGCTAATGGCGCCTACTGCATCGCCCTGAAAGGATTGTATGAAATTAAGCAGA TTACAGAAAATTGGAAGGAAGATGGTAAATTTAGCCGTGATAAATTAAAAATCTCG AACAAGGATTGGTTCGATTTTATTCAGAACAAACGTTATTTGAAACGTCCGGCAGCG ACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCA GCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCG GGCTAA SEQ ID NO: 50 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA CAATGGAACAAATAATTTTCAAAATTTTATCGGCATCTCAAGTCTTCAAAAAACCCT TCGCAATGCCCTGATTCCAACTGAAACAACCCAGCAATTTATCGTCAAGAACGGCAT CATTAAGGAAGACGAGTTACGCGGGGAGAACCGTCAAATCCTGAAAGATATCATGG ATGACTACTATCGTGGGTTCATTTCGGAAACCTTGTCTTCAATCGACGACATTGACT GGACGAGTCTTTTCGAGAAAATGGAAATTCAGCTTAAAAATGGAGACAACAAGGAT ACTCTGATTAAGGAACAGACAGAATATCGCAAAGCTATCCACAAAAAGTTCGCTAA TGATGATCGTTTCAAAAATATGTTTTCTGCTAAATTGATTTCCGATATCTTGCCTGAA TTTGTAATCCACAACAACAATTATTCTGCTTCCGAGAAGGAAGAGAAGACCCAGGTC ATTAAATTATTCAGCCGCTTTGCAACCAGCTTTAAAGACTACTTTAAGAATCGCGCT AACTGCTTTTCGGCGGATGACATCTCATCATCATCATGCCACCGCATTGTGAACGAC AATGCGGAGATCTTCTTTTCGAATGCGTTAGTTTATCGTCGCATTGTCAAAAGTCTTA GCAATGATGACATCAACAAGATCTCAGGAGACATGAAAGATTCCTTAAAGGAGATG TCTCTTGAGGAAATCTATTCGTATGAGAAATACGGCGAGTTCATTACCCAGGAAGGT ATTAGTTTCTACAATGATATCTGCGGCAAAGTAAATTCTTTTATGAATCTGTATTGCC AAAAAAACAAAGAAAACAAGAATCTTTATAAGTTACAAAAGTTACATAAGCAAATT CTGTGCATCGCTGATACATCTTATGAGGTACCCTACAAATTTGAAAGTGATGAGGAG GTCTATCAGAGTGTCAACGGCTTCTTAGACAACATCTCTTCCAAACATATCGTGGAA CGCCTGCGTAAAATCGGAGATAACTACAACGGATATAACTTAGATAAAATCTACAT CGTGTCCAAGTTTTATGAAAGTGTGAGCCAAAAAACATATCGTGACTGGGAAACCA TTAACACCGCATTGGAAATTCACTATAACAACATTTTGCCAGGCAACGGGAAAAGT AAGGCGGACAAAGTTAAGAAAGCAGTTAAAAATGACCTGCAAAAAAGCATCACTG AAATTAACGAATTGGTATCGAATTACAAATTATGTAGCGACGATAATATCAAAGCA GAAACTTACATTCACGAGATTAGTCACATTTTAAATAACTTCGAGGCCCAGGAATTG AAATACAATCCCGAAATTCATTTGGTTGAATCAGAACTGAAAGCATCAGAGTTGAA AAATGTGTTAGATGTCATTATGAATGCGTTTCATTGGTGCTCTGTGTTCATGACCGAG GAACTGGTTGATAAAGATAACAACTTTTACGCTGAATTGGAGGAGATTTACGATGA GATTTACCCGGTCATTTCGCTTTATAACTTAGTGCGCAATTATGTGACGCAGAAACC ATATTCCACGAAGAAAATCAAACTTAATTTTGGCATCCCTACTCTGGCTGATGGTTG GTCGAAATCGAAAGAGTACAGCAACAACGCGATCATTCTTATGCGTGACAATCTTTA CTATTTGGGCATTTTTAATGCCAAGAATAAGCCAGATAAGAAAATCATTGAGGGGA ATACTTCCGAGAATAAGGGGGATTACAAAAAGATGATCTATAACTTGCTGCCCGGC CCCAACAAAATGATTCCTAAGGTTTTCTTGTCAAGCAAGACGGGCGTCGAAACATAT AAGCCGTCAGCTTATATTCTGGAAGGCTATAAACAGAATAAGCACATCAAGTCTTCC AAGGACTTTGACATCACTTTTTGCCACGATTTGATCGACTACTTTAAGAACTGTATTG CGATTCATCCGGAATGGAAGAACTTCGGTTTCGACTTTTCCGATACCTCAACATACG AGGATATCAGCGGCTTCTACCGTGAAGTCGAGCTTCAAGGCTACAAGATCGATTGG ACATATATTTCAGAGAAGGACATTGATTTGTTACAAGAGAAAGGTCAACTTTACTTA TTTCAGATCTATAACAAAGACTTTTCGAAGAAATCGACAGGAAACGATAACTTACAC ACTATGTATTTAAAAAATCTGTTTTCGGAGGAAAACCTGAAAGATATTGTGCTGAAA CTTAACGGCGAGGCAGAGATCTTTTTCCGTAAAAGCTCAATCAAGAATCCTATCATC CATAAAAAAGGTAGTATTCTTGTCAACCGCACATATGAAGCGGAGGAGAAGGACCA ATTCGGAAACATCCAAATTGTCCGTAAGAATATTCCGGAGAACATTTACCAAGAGTT GTATAAATACTTTAACGATAAGTCAGATAAGGAACTTAGCGATGAGGCGGCGAAGC TTAAAAACGTAGTTGGGCATCATGAAGCTGCTACCAACATTGTAAAAGATTACCGTT ACACCTATGACAAGTATTTCTTGCACATGCCCATTACGATCAATTTCAAAGCAAATA AGACAGGCTTTATCAATGATCGCATCCTGCAGTACATTGCTAAAGAGAAGGATTTGC ATGTTATCGGTATTGATCGCGGAGAGCGCAATTTGATCTACGTCTCCGTAATCGACA CTTGCGGTAACATTGTTGAGCAGAAGTCGTTCAACATCGTTAATGGTTATGATTACC AAATCAAGCTGAAGCAGCAAGAGGGTGCCCGCCAGATCGCGCGTAAGGAATGGAA AGAAATCGGGAAAATTAAAGAGATCAAAGAAGGCTATTTGTCTCTGGTAATTCACG AAATCAGCAAGATGGTGATCAAGTATAACGCGATCATTGCGATGGAGGATCTTTCTT ATGGCTTCAAGAAAGGGCGCTTTAAAGTCGAACGCCAGGTCTACCAGAAATTTGAG ACAATGCTTATCAACAAGCTTAACTATCTTGTATTTAAGGATATTTCCATCACTGAG AACGGAGGACTTTTAAAGGGGTACCAACTGACGTACATTCCTGATAAGCTGAAGAA CGTTGGTCATCAATGCGGATGCATCTTCTATGTGCCAGCGGCTTACACCTCCAAAAT CGATCCCACTACAGGCTTTGTCAATATCTTCAAATTCAAGGATTTGACCGTTGACGC GAAGCGCGAGTTTATCAAGAAGTTTGATAGCATTCGCTACGACAGCGAAAAAAATT TATTTTGTTTTACTTTCGACTACAATAACTTTATTACTCAGAACACTGTCATGTCAAA GAGTTCGTGGAGTGTCTACACGTACGGAGTACGTATTAAGCGCCGTTTCGTCAACGG ACGCTTCTCAAACGAAAGCGACACGATCGACATCACCAAAGACATGGAAAAAACTC TTGAGATGACGGATATCAATTGGCGCGACGGCCATGACCTGCGTCAGGATATCATTG ATTACGAGATCGTTCAGCACATCTTCGAAATCTTCCGCCTTACCGTCCAGATGCGCA ACAGTTTAAGCGAGCTTGAAGACCGCGACTACGATCGTTTGATTAGCCCCGTTCTGA ACGAGAATAATATTTTCTACGACAGCGCAAAGGCCGGTGATGCTTTGCCAAAGGAC GCAGACGCGAATGGAGCCTACTGCATCGCCCTGAAGGGCTTATATGAGATTAAGCA AATTACCGAAAATTGGAAGGAAGATGGTAAGTTCTCCCGTGATAAGCTTAAAATTA GCAATAAGGATTGGTTCGACTTCATCCAGAACAAACGTTACCTGAAACGTCCGGCA GCGACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAG GCAGCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTAT TCCGGGCTAA SEQ ID NO: 51 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA CAACGGAACAAACAATTTCCAAAACTTCATCGGTATCTCTTCGTTGCAGAAGACTCT GCGTAATGCTTTGATCCCGACGGAGACAACCCAACAATTTATCGTCAAAAACGGTAT TATTAAGGAGGACGAGTTACGTGGAGAAAATCGTCAAATCCTTAAGGACATCATGG ACGATTATTATCGCGGGTTTATTTCTGAAACCCTGAGCAGTATCGATGATATCGACT GGACCTCACTTTTTGAGAAAATGGAGATCCAGTTGAAGAACGGTGATAACAAAGAC ACTCTGATCAAAGAGCAAACTGAATACCGCAAGGCAATTCACAAAAAGTTCGCCAA CGACGACCGTTTCAAGAATATGTTCTCAGCTAAGTTAATCAGCGACATTTTGCCAGA GTTCGTTATCCACAACAATAATTATAGTGCTTCAGAGAAGGAGGAAAAAACCCAAG TGATTAAACTTTTTTCGCGCTTTGCAACCTCATTCAAGGACTACTTCAAGAATCGCGC GAATTGCTTCAGTGCGGACGACATTTCTTCTTCAAGTTGCCATCGTATCGTTAACGAT AACGCGGAAATTTTCTTCTCTAATGCTTTGGTGTATCGCCGCATTGTAAAATCGCTTA GTAACGATGACATTAATAAGATCTCAGGTGATATGAAAGATTCATTGAAGGAAATG AGCTTGGAAGAGATTTACAGTTACGAAAAATATGGAGAATTTATTACTCAGGAAGG CATCTCATTCTATAACGATATCTGCGGGAAGGTAAATTCGTTTATGAACTTATATTGC CAGAAAAATAAAGAGAATAAAAATTTGTATAAGCTTCAGAAGTTGCACAAACAGAT CCTGTGCATTGCAGACACCTCGTATGAGGTTCCGTATAAATTTGAGTCCGATGAAGA AGTGTATCAGTCTGTGAATGGTTTCTTAGATAATATCTCTTCCAAGCATATTGTCGAA CGCCTGCGCAAAATTGGTGATAACTATAACGGATACAATCTGGATAAAATTTACATC GTTTCTAAATTTTACGAGTCAGTCTCGCAGAAGACCTACCGCGACTGGGAAACAATT AACACGGCATTGGAGATTCACTACAATAATATCTTGCCTGGTAACGGTAAGTCTAAG GCAGATAAGGTAAAAAAAGCTGTGAAAAACGACCTTCAGAAAAGCATCACGGAGA TTAATGAGCTGGTGAGTAATTACAAATTATGTTCAGACGATAATATTAAAGCTGAAA CGTATATCCATGAAATCTCGCATATCTTGAACAACTTCGAGGCCCAAGAACTTAAAT ATAACCCCGAAATCCATTTAGTCGAGTCTGAATTGAAAGCGTCGGAATTAAAAAAC GTCTTAGACGTCATTATGAACGCGTTTCACTGGTGTTCAGTTTTCATGACCGAAGAG CTGGTCGACAAAGACAACAACTTCTATGCGGAATTGGAGGAAATCTATGATGAAAT CTACCCTGTTATTTCACTGTATAACCTTGTGCGCAACTATGTCACTCAGAAGCCGTAT TCGACCAAAAAAATTAAATTGAATTTCGGTATCCCTACTCTTGCAGACGGATGGAGT AAAAGCAAGGAATACAGTAATAACGCCATTATTCTTATGCGCGACAATTTATACTAC CTGGGCATCTTTAACGCAAAGAATAAGCCGGATAAGAAGATTATTGAGGGTAACAC CAGTGAGAACAAGGGCGACTATAAGAAGATGATCTATAACTTATTGCCAGGTCCAA ATAAAATGATCCCAAAAGTATTCTTATCATCAAAGACGGGAGTTGAAACCTATAAG CCTAGTGCCTATATTCTTGAGGGATATAAACAGAACAAGCACATTAAGTCGTCTAAG GATTTTGACATTACGTTCTGCCATGACTTAATCGACTATTTTAAAAACTGTATTGCGA TTCACCCCGAATGGAAGAATTTTGGATTCGATTTTTCGGATACCTCGACCTATGAAG ATATTTCGGGATTTTATCGTGAAGTGGAGTTGCAAGGCTATAAAATCGATTGGACCT ATATCTCAGAAAAAGACATTGATTTATTACAGGAAAAGGGACAACTGTACCTTTTCC AAATTTATAACAAGGACTTTTCTAAAAAGTCCACAGGAAATGATAACCTTCACACCA TGTACCTGAAGAACCTTTTCTCAGAGGAAAACCTGAAGGACATTGTCCTTAAGTTAA ATGGAGAAGCGGAGATCTTTTTCCGTAAATCTAGTATCAAGAATCCGATTATCCATA AAAAAGGTTCGATTTTGGTAAATCGCACCTATGAAGCGGAAGAGAAAGATCAATTT GGTAACATCCAGATCGTGCGCAAGAATATCCCGGAGAACATTTACCAAGAGCTGTA TAAGTACTTCAATGATAAGTCTGATAAGGAACTGTCAGATGAAGCTGCGAAATTGA AGAACGTGGTTGGGCATCATGAAGCCGCTACCAATATCGTCAAGGATTACCGTTATA CCTATGACAAATATTTCTTACACATGCCGATTACGATCAATTTTAAGGCAAACAAGA CAGGATTCATCAACGACCGTATCTTGCAGTATATTGCCAAAGAGAAGGATCTGCATG TGATCGGTATTGACCGCGGGGAGCGCAATTTAATCTATGTATCGGTGATCGATACTT GTGGTAACATCGTAGAACAAAAGAGCTTTAACATCGTGAATGGTTACGACTATCAG ATCAAGCTGAAACAACAGGAAGGAGCCCGCCAGATCGCTCGCAAGGAATGGAAAG AAATCGGGAAAATTAAGGAAATCAAGGAAGGCTACCTTTCATTGGTCATTCACGAA ATTTCGAAAATGGTAATTAAGTACAACGCGATCATCGCCATGGAGGACCTTTCGTAC GGATTTAAGAAGGGTCGTTTCAAAGTTGAGCGCCAGGTATACCAAAAATTCGAGAC TATGCTTATCAACAAACTTAACTACTTGGTCTTTAAGGACATTTCTATTACCGAAAAC GGCGGCTTACTTAAAGGCTATCAATTGACATATATTCCCGACAAACTGAAGAATGTT GGACATCAATGCGGGTGTATTTTCTATGTGCCGGCAGCTTACACTAGTAAGATCGAC CCTACAACCGGGTTCGTAAACATTTTTAAATTCAAAGACTTAACAGTCGATGCGAAG CGTGAATTTATTAAGAAGTTTGATAGTATCCGCTATGACAGTGAAAAGAACTTGTTT TGCTTTACGTTCGACTACAATAACTTTATTACACAGAACACGGTCATGTCTAAATCA TCATGGTCGGTTTACACATATGGGGTGCGCATCAAGCGTCGCTTTGTAAATGGCCGT TTTAGTAATGAGAGCGACACAATCGACATCACAAAGGATATGGAGAAAACTCTTGA GATGACAGACATCAATTGGCGTGACGGTCATGACTTACGCCAAGATATCATCGACTA CGAAATCGTACAGCATATTTTTGAGATTTTTCGTCTTACTGTGCAAATGCGTAATTCT TTATCCGAACTGGAAGATCGTGATTACGACCGCTTGATTAGTCCCGTCTTAAATGAG AACAATATTTTCTATGATTCTGCGAAAGCCGGAGATGCACTGCCCAAAGACGCTGAT GCCAATGGCGCGTATTGCATTGCATTAAAAGGATTATATGAGATTAAACAGATTACC GAAAATTGGAAAGAGGACGGTAAATTCTCACGCGATAAATTGAAGATTTCTAACAA GGACTGGTTCGACTTTATCCAAAATAAACGTTATCTTAAACGTCCGGCAGCGACCAA AAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCG AAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTA A SEQ ID NO: 52 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA TAACGGTACCAACAACTTTCAGAATTTCATTGGCATTAGCTCGCTTCAAAAAACTTT ACGCAATGCTCTTATTCCGACTGAGACGACACAACAGTTTATCGTTAAGAATGGCAT CATCAAAGAAGATGAATTACGCGGAGAAAACCGCCAGATCCTGAAAGACATTATGG ACGATTATTACCGTGGGTTCATCTCCGAGACGTTGTCATCGATCGATGACATCGACT GGACGTCACTTTTTGAAAAAATGGAGATCCAGTTAAAGAACGGTGACAATAAGGAT ACATTGATCAAAGAACAGACCGAGTACCGTAAAGCGATTCATAAAAAGTTTGCGAA CGATGATCGCTTCAAGAATATGTTTTCTGCGAAATTAATTTCCGACATTTTACCTGAA TTTGTTATTCATAATAACAACTACTCGGCGTCTGAGAAAGAGGAGAAAACCCAAGT GATTAAACTTTTTTCACGTTTCGCAACGTCGTTCAAAGACTATTTTAAAAATCGTGCT AATTGCTTTAGCGCGGATGACATCAGCTCTAGTTCATGTCATCGCATTGTCAACGAT AATGCTGAGATCTTTTTCAGTAATGCGTTAGTGTACCGTCGTATTGTGAAGTCCTTAT CTAATGATGATATCAATAAGATCAGCGGGGATATGAAGGACTCACTTAAGGAGATG AGCTTGGAGGAAATCTATTCCTATGAGAAGTATGGTGAGTTTATTACGCAAGAAGG AATTAGCTTTTACAACGATATCTGTGGAAAGGTGAATTCGTTTATGAATTTGTATTGC CAGAAAAATAAGGAGAACAAGAACCTTTATAAATTGCAAAAGTTACACAAGCAAAT CCTGTGCATTGCAGATACTTCCTACGAGGTGCCTTACAAGTTTGAATCCGACGAAGA GGTCTACCAATCTGTAAACGGTTTCTTAGATAATATTAGTTCCAAGCATATTGTGGA GCGCCTTCGTAAAATTGGCGATAATTACAACGGTTACAATTTAGACAAAATTTACAT TGTCAGTAAATTCTACGAGTCCGTATCTCAAAAGACGTATCGTGATTGGGAGACTAT CAATACGGCCCTGGAGATCCACTACAACAATATCTTGCCCGGTAATGGTAAGTCGAA GGCCGATAAAGTTAAGAAAGCGGTGAAAAATGACTTACAGAAGTCAATCACCGAAA TTAACGAATTGGTGTCCAATTATAAATTGTGTTCAGATGATAATATCAAAGCCGAGA CCTACATTCATGAGATTTCCCATATCTTAAATAATTTCGAGGCGCAAGAGCTTAAGT ATAACCCAGAAATCCACCTGGTAGAATCTGAGTTGAAGGCGTCAGAGTTAAAAAAT GTTTTAGATGTCATTATGAACGCGTTTCACTGGTGCTCCGTATTTATGACGGAGGAA TTAGTAGATAAAGACAACAATTTCTATGCCGAACTTGAGGAAATCTATGATGAGATC TATCCCGTCATTAGCCTGTATAACTTGGTCCGCAACTATGTTACCCAAAAACCGTAC AGTACCAAGAAGATTAAGCTGAATTTCGGCATTCCTACACTGGCTGATGGTTGGAGT AAATCGAAGGAATATTCGAATAACGCGATTATCTTGATGCGCGACAACTTATACTAT TTGGGGATCTTTAACGCCAAAAACAAACCGGATAAGAAGATTATTGAGGGAAACAC ATCAGAGAACAAAGGCGACTACAAAAAAATGATTTACAACTTGTTACCGGGGCCTA ACAAAATGATCCCGAAGGTGTTCTTATCCAGTAAAACAGGCGTTGAGACCTACAAA CCTTCCGCATACATCCTGGAAGGGTATAAGCAGAACAAGCACATTAAGTCCAGCAA GGATTTCGATATTACCTTCTGTCATGATTTAATTGACTATTTCAAGAACTGTATTGCA ATCCACCCCGAGTGGAAGAACTTCGGATTCGACTTCTCAGATACGAGCACATATGAG GACATCTCGGGGTTCTATCGTGAAGTAGAACTGCAGGGATATAAAATTGATTGGAC ATATATTTCCGAAAAAGACATCGACCTTTTACAAGAGAAGGGTCAACTTTACTTGTT CCAAATTTACAATAAAGACTTCTCAAAAAAAAGCACGGGTAACGATAATTTACACA CTATGTATTTAAAGAACCTTTTCTCGGAAGAGAATTTAAAGGATATCGTATTGAAGT TGAATGGAGAAGCGGAGATCTTCTTCCGTAAGTCCAGTATTAAAAACCCTATTATTC ACAAGAAGGGATCGATTTTAGTTAACCGCACATACGAGGCCGAAGAGAAGGACCAA TTTGGGAACATTCAAATTGTCCGCAAAAACATCCCTGAGAACATTTATCAAGAGCTT TATAAGTACTTTAACGATAAGTCCGATAAGGAATTGTCAGATGAGGCGGCAAAGTT GAAGAATGTCGTGGGGCATCATGAAGCTGCCACCAACATTGTGAAGGACTACCGCT ACACTTACGACAAATACTTCCTGCACATGCCCATTACGATCAATTTTAAGGCCAATA AGACAGGCTTTATTAACGACCGTATTCTTCAATATATCGCTAAGGAGAAGGACCTTC ATGTGATTGGGATCGACCGCGGAGAACGTAATTTAATTTATGTGTCCGTCATCGATA CGTGTGGAAATATCGTGGAACAGAAATCATTCAATATCGTGAATGGCTATGATTACC AGATCAAATTAAAACAGCAGGAGGGCGCTCGCCAAATTGCGCGTAAGGAATGGAAA GAGATCGGAAAAATCAAAGAAATCAAAGAAGGATATTTGTCATTGGTGATCCATGA GATTTCAAAAATGGTAATTAAATATAATGCAATTATCGCAATGGAAGACCTGTCCTA TGGTTTTAAGAAGGGTCGTTTCAAGGTAGAACGCCAAGTGTATCAAAAGTTCGAGA CGATGCTGATCAATAAGCTGAATTATCTTGTGTTTAAGGACATTAGCATCACGGAAA ATGGAGGGCTGTTGAAAGGCTATCAACTGACGTATATCCCTGACAAGCTGAAAAAT GTTGGCCATCAGTGCGGGTGCATTTTCTACGTCCCCGCGGCGTATACAAGCAAGATC GATCCTACTACGGGATTCGTAAATATTTTTAAATTCAAAGACTTAACCGTGGACGCC AAGCGCGAATTCATTAAGAAGTTTGATAGCATTCGCTACGATTCAGAAAAAAATCTT TTCTGTTTTACGTTCGATTACAACAATTTTATCACCCAGAACACAGTGATGAGCAAG TCATCCTGGTCTGTCTATACCTACGGTGTCCGTATCAAACGCCGCTTCGTCAACGGA CGCTTCTCTAATGAATCTGATACCATTGACATCACCAAGGACATGGAAAAGACACTT GAGATGACAGATATTAACTGGCGTGACGGACATGACCTGCGTCAGGACATCATCGA TTATGAGATTGTTCAGCATATCTTCGAGATCTTCCGCCTGACAGTACAAATGCGCAA TTCACTGTCAGAACTTGAAGACCGCGACTATGACCGCCTGATCTCTCCAGTATTAAA TGAGAACAATATCTTTTATGACAGTGCTAAGGCCGGCGATGCCCTTCCGAAAGATGC TGATGCTAACGGAGCTTATTGTATTGCATTAAAGGGTCTTTATGAGATCAAGCAAAT TACCGAGAATTGGAAGGAGGATGGCAAATTCTCGCGCGACAAACTGAAAATCAGTA ACAAGGACTGGTTCGATTTTATTCAGAATAAACGTTACCTGAAACGTCCGGCAGCGA CCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAG CCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGG GCTAA SEQ ID NO: 53 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA TAACGGAACGAACAACTTCCAGAACTTCATCGGCATCAGTTCTTTACAAAAAACCCT GCGTAACGCCCTTATTCCGACTGAGACAACACAACAGTTCATCGTTAAAAACGGAAT TATCAAAGAGGACGAGTTGCGCGGCGAGAATCGCCAAATTTTGAAAGATATTATGG ACGACTATTATCGTGGTTTTATTTCAGAAACACTGAGTTCGATTGACGATATCGATT GGACGAGCCTGTTTGAGAAAATGGAAATCCAGTTGAAAAATGGCGATAATAAAGAC ACTTTAATCAAAGAACAAACCGAGTATCGTAAAGCGATCCATAAAAAGTTCGCTAA TGACGATCGTTTTAAGAATATGTTCAGTGCGAAACTGATTTCAGACATTTTGCCCGA GTTCGTGATCCATAATAACAACTATTCCGCCTCGGAAAAGGAAGAAAAAACCCAGG TGATTAAGCTGTTCAGTCGCTTCGCAACATCTTTCAAGGATTATTTCAAGAATCGCG CGAATTGCTTCAGTGCGGACGATATTTCTAGTTCAAGCTGCCATCGTATCGTTAATG ATAACGCGGAGATTTTTTTTAGCAATGCTCTGGTGTACCGCCGCATTGTTAAGTCACT GTCCAACGATGATATTAACAAGATCTCAGGAGACATGAAAGACTCGCTTAAAGAGA TGAGTCTGGAAGAGATCTATTCTTATGAGAAGTATGGCGAGTTTATTACCCAAGAAG GAATCTCATTCTACAATGATATTTGTGGAAAGGTGAACAGCTTTATGAATCTTTACT GCCAAAAAAACAAGGAGAATAAGAATCTTTACAAACTTCAGAAGTTACATAAACAG ATTTTGTGTATTGCGGATACGTCTTATGAAGTCCCCTACAAATTTGAATCGGATGAA GAGGTATACCAAAGTGTGAACGGATTCTTGGACAATATTTCTTCTAAACATATTGTT GAACGCTTACGTAAGATCGGGGATAACTACAATGGCTACAATCTTGACAAAATCTA CATTGTTAGCAAATTCTACGAGAGTGTCAGCCAAAAGACGTACCGCGATTGGGAAA CAATTAATACTGCGCTTGAGATTCACTATAATAACATTTTACCAGGCAACGGCAAGT CCAAGGCGGATAAAGTTAAAAAAGCTGTTAAAAACGATTTGCAAAAATCTATCACA GAAATTAACGAGTTAGTTAGTAACTACAAACTGTGCTCCGATGACAACATTAAGGCT GAGACGTATATCCATGAGATCTCTCACATCTTAAACAATTTTGAAGCTCAAGAACTT AAGTACAATCCGGAAATCCACCTGGTGGAATCCGAGCTGAAGGCTAGCGAACTGAA GAACGTATTGGACGTGATCATGAACGCGTTCCACTGGTGTTCTGTCTTTATGACGGA AGAGCTTGTCGACAAAGATAATAACTTTTACGCGGAACTTGAGGAAATTTACGATG AGATTTACCCAGTTATTTCATTGTATAACCTTGTCCGTAATTACGTGACCCAAAAGCC TTATAGTACGAAAAAAATCAAATTAAATTTTGGAATCCCAACACTGGCTGACGGTTG GAGCAAATCTAAGGAGTATTCTAATAACGCAATCATCTTAATGCGTGACAACCTGTA TTATTTGGGTATCTTCAATGCCAAAAATAAGCCTGACAAAAAGATTATCGAAGGAA ATACTTCGGAGAATAAGGGGGATTACAAAAAAATGATTTACAATTTGCTGCCCGGG CCGAACAAGATGATCCCCAAAGTGTTCTTATCCTCGAAGACTGGTGTAGAAACATAC AAGCCAAGCGCATACATTCTGGAGGGTTACAAGCAAAACAAACACATCAAATCTTC AAAAGACTTTGACATTACATTTTGCCATGATCTTATTGACTACTTCAAAAACTGCATT GCTATTCACCCCGAGTGGAAGAACTTTGGGTTTGACTTCAGCGACACGTCTACGTAT GAGGACATCTCCGGGTTCTACCGTGAAGTTGAGTTACAAGGGTATAAGATTGACTGG ACGTATATTTCAGAGAAAGATATCGATCTTTTGCAGGAAAAGGGCCAGTTATATTTA TTCCAGATTTACAACAAGGACTTTAGTAAGAAGTCAACAGGAAATGACAACTTGCA TACGATGTATTTGAAAAATCTTTTTTCTGAGGAAAATCTTAAGGACATCGTACTGAA ATTGAATGGCGAGGCTGAAATCTTCTTCCGTAAATCCTCCATTAAGAATCCCATTAT CCACAAAAAGGGGTCTATCCTGGTGAATCGTACCTACGAGGCAGAGGAGAAGGATC AATTCGGAAATATTCAGATTGTTCGTAAGAACATCCCCGAGAACATTTATCAAGAAT TGTATAAGTACTTTAATGACAAATCTGACAAAGAGTTATCCGACGAAGCTGCGAAA CTGAAAAACGTTGTTGGTCACCACGAGGCCGCCACTAATATCGTAAAAGACTACCGT TATACCTATGACAAGTACTTTTTGCACATGCCGATCACTATCAACTTCAAGGCGAAT AAGACGGGCTTCATTAACGATCGTATCCTGCAATACATCGCCAAGGAGAAGGACCT TCACGTCATTGGGATTGACCGTGGTGAGCGTAACCTGATTTATGTAAGCGTCATTGA TACCTGCGGTAATATCGTCGAACAGAAAAGTTTCAACATTGTAAATGGATATGACTA TCAGATCAAACTTAAGCAGCAGGAGGGTGCACGCCAGATTGCCCGCAAGGAATGGA AGGAGATTGGGAAGATTAAGGAAATTAAAGAAGGTTACTTATCACTGGTTATTCAC GAGATCAGTAAAATGGTAATCAAATATAACGCGATCATTGCCATGGAGGATCTGAG CTATGGCTTTAAAAAGGGCCGTTTCAAAGTCGAGCGCCAGGTATATCAAAAGTTTGA AACAATGCTGATTAACAAATTAAACTATCTGGTTTTCAAAGATATTTCGATCACTGA AAATGGCGGGCTGTTGAAGGGATACCAACTTACATACATCCCTGACAAACTGAAAA ATGTCGGTCACCAATGTGGATGTATCTTTTATGTACCAGCAGCGTATACGAGCAAAA TCGATCCAACTACGGGTTTTGTGAACATCTTTAAGTTCAAGGATTTGACAGTAGATG CCAAACGCGAGTTCATTAAAAAATTTGATTCAATTCGCTACGATTCAGAGAAAAATC TTTTTTGTTTCACGTTCGATTACAATAATTTCATTACGCAGAACACAGTAATGTCAAA GTCAAGCTGGTCGGTCTACACGTATGGAGTCCGTATTAAACGTCGTTTTGTAAACGG CCGTTTCTCAAATGAATCAGATACAATTGATATTACGAAGGATATGGAGAAGACATT AGAGATGACTGACATTAACTGGCGCGACGGACATGATCTTCGTCAGGACATTATTGA TTATGAGATTGTACAGCATATCTTTGAGATCTTCCGCCTGACCGTTCAGATGCGCAA TTCGTTGTCCGAGTTAGAAGACCGCGATTACGACCGTTTAATCAGTCCCGTCTTAAA CGAAAATAACATCTTCTACGATTCAGCCAAGGCAGGCGATGCCTTGCCAAAGGATG CTGACGCAAATGGCGCATACTGTATTGCGTTGAAAGGCCTTTATGAAATCAAGCAAA TTACCGAAAACTGGAAAGAAGACGGAAAATTCTCCCGTGATAAGTTGAAAATCTCT AATAAGGATTGGTTCGATTTCATCCAAAATAAACGCTATTTGAAACGTCCGGCAGCG ACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCA GCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCG GGCTAA SEQ ID NO: 54 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA CAACGGAACTAATAATTTCCAAAATTTTATAGGCATCTCTTCTTTACAGAAGACTCTT CGTAACGCCCTAATCCCGACTGAGACCACACAACAATTCATAGTGAAAAATGGGAT CATTAAAGAAGACGAGCTGCGTGGGGAGAACAGGCAGATCCTAAAAGACATAATG GACGATTATTATAGAGGGTTCATCTCAGAGACATTATCTAGCATCGACGACATTGAC TGGACCTCCCTGTTTGAAAAAATGGAAATCCAGCTGAAGAATGGTGACAATAAAGA CACATTAATAAAAGAACAAACAGAGTACAGGAAAGCCATCCACAAGAAGTTCGCAA ACGATGACAGATTCAAAAATATGTTCAGTGCGAAGCTAATATCCGACATCTTACCAG AGTTTGTAATACACAATAACAATTACAGCGCGAGCGAAAAGGAAGAGAAAACGCA AGTAATTAAGCTTTTTAGTAGGTTCGCTACCTCTTTCAAAGATTACTTCAAAAATCGT GCTAACTGCTTCTCAGCCGACGACATATCTTCAAGTTCCTGTCACCGTATCGTGAAT GATAACGCTGAGATATTCTTCTCAAACGCCCTTGTATACCGTAGGATCGTAAAGTCC TTATCTAACGATGATATAAACAAGATCAGTGGAGACATGAAAGACAGCCTTAAAGA GATGTCTCTAGAAGAAATTTACTCCTATGAAAAGTATGGGGAGTTTATAACACAGGA GGGGATCAGCTTCTACAACGACATCTGCGGAAAGGTGAACAGTTTCATGAATCTTTA CTGCCAGAAGAATAAAGAGAACAAAAATCTTTATAAGCTTCAAAAGTTGCACAAAC AAATACTGTGCATTGCCGATACATCATATGAGGTCCCCTATAAGTTCGAATCTGATG AGGAAGTTTATCAATCTGTTAACGGCTTTCTAGACAATATCAGCTCAAAACACATCG TAGAAAGACTGAGGAAAATAGGTGATAATTATAATGGATACAACTTGGATAAAATA TATATAGTCTCTAAATTTTACGAGTCAGTATCCCAGAAAACGTATAGGGATTGGGAG ACCATCAACACGGCGTTAGAGATTCATTACAATAACATCTTACCGGGAAACGGAAA AAGTAAGGCGGACAAAGTAAAGAAAGCCGTTAAAAATGACTTACAAAAGAGTATA ACAGAAATAAACGAACTAGTAAGCAACTACAAGCTTTGTTCCGATGATAATATCAA GGCCGAGACATATATCCATGAGATCTCCCACATTCTAAACAATTTCGAAGCGCAAGA ACTTAAATATAATCCCGAAATCCACCTGGTGGAAAGTGAACTAAAGGCTAGTGAGT TAAAGAACGTTCTTGATGTTATCATGAACGCCTTCCATTGGTGCTCTGTTTTTATGAC CGAGGAGTTGGTTGATAAAGATAATAATTTCTACGCTGAATTAGAGGAGATATACG ACGAAATCTACCCAGTGATTTCACTATACAACTTGGTCAGGAACTATGTTACACAAA AGCCGTACAGCACTAAGAAAATTAAGCTAAATTTCGGTATCCCCACGTTAGCCGACG GGTGGAGCAAGTCCAAAGAATATTCCAACAATGCGATTATTTTAATGCGTGACAATC TTTATTACCTTGGCATCTTCAATGCCAAAAACAAACCTGACAAAAAGATTATAGAAG GTAATACGTCCGAGAACAAAGGCGATTACAAGAAGATGATTTATAACCTACTGCCC GGACCAAACAAAATGATCCCCAAAGTTTTTCTTAGTTCTAAAACCGGCGTAGAGACG TATAAACCTTCTGCCTATATCTTAGAGGGATATAAGCAGAACAAACATATCAAATCT TCCAAGGACTTTGATATTACATTCTGCCACGATTTAATTGACTACTTCAAAAATTGCA TAGCGATACATCCGGAGTGGAAGAACTTTGGCTTCGACTTCAGTGATACATCCACCT ATGAGGATATATCAGGCTTCTATCGTGAGGTCGAATTGCAAGGGTACAAAATCGATT GGACGTATATATCCGAGAAAGACATAGACCTTCTTCAAGAAAAGGGGCAGTTATAT TTATTCCAAATATACAACAAGGACTTCAGTAAGAAGTCAACAGGTAATGACAACTT ACACACCATGTACTTGAAAAATTTATTTTCTGAAGAAAACCTAAAGGACATTGTACT AAAACTGAACGGGGAGGCAGAAATTTTTTTTAGAAAGAGCAGCATAAAAAACCCAA TAATTCATAAGAAAGGAAGCATTTTAGTTAATAGGACGTACGAGGCAGAGGAAAAG GACCAGTTTGGCAATATCCAGATCGTAAGGAAAAATATTCCTGAAAACATATATCA GGAACTATATAAATACTTTAACGACAAATCCGACAAAGAATTATCCGACGAGGCTG CAAAGCTGAAGAACGTCGTAGGGCACCATGAGGCAGCGACTAATATTGTGAAAGAC TATAGGTATACATACGACAAATACTTTCTGCACATGCCCATCACGATTAACTTCAAG GCGAACAAGACGGGATTCATTAACGACCGTATATTACAATATATTGCTAAGGAGAA AGATCTGCATGTAATAGGTATCGACAGAGGCGAACGTAATTTAATCTACGTGTCCGT CATCGACACGTGCGGGAACATCGTAGAGCAAAAGAGTTTTAATATAGTAAATGGCT ATGATTACCAAATTAAGCTAAAGCAGCAAGAAGGAGCAAGACAGATAGCTAGGAA AGAATGGAAGGAGATAGGAAAAATAAAGGAGATCAAGGAGGGGTATCTTAGCCTA GTAATTCATGAAATATCTAAGATGGTTATCAAATACAACGCTATCATAGCGATGGAA GACTTATCTTATGGTTTCAAGAAAGGAAGGTTCAAAGTAGAGCGTCAAGTTTATCAA AAGTTCGAAACGATGTTGATTAATAAACTAAACTATTTGGTATTTAAAGATATATCT ATCACCGAGAATGGTGGTCTACTAAAGGGTTACCAGCTTACATACATACCGGACAA ACTTAAAAACGTCGGACATCAGTGTGGATGCATTTTCTACGTTCCAGCTGCATATAC CAGCAAGATCGACCCAACGACTGGGTTCGTAAATATTTTTAAATTCAAGGATTTGAC TGTCGACGCCAAAAGAGAGTTCATAAAAAAGTTCGATTCAATTAGGTACGACAGCG AAAAGAATTTGTTCTGCTTTACTTTTGACTATAACAATTTCATTACTCAGAACACTGT AATGTCTAAGTCCTCTTGGTCAGTCTATACTTATGGCGTTCGTATCAAACGTAGATTT GTTAACGGTAGATTCTCAAATGAAAGTGATACAATAGATATCACGAAAGATATGGA GAAAACATTAGAAATGACAGACATAAACTGGAGAGACGGACATGACTTGAGACAG GACATTATTGACTACGAGATCGTGCAGCACATCTTTGAGATCTTTCGTTTGACCGTA CAAATGCGTAACAGTTTATCTGAGCTTGAGGACAGGGACTACGATAGATTGATATCA CCTGTATTAAATGAGAATAACATCTTCTATGATTCCGCAAAAGCAGGCGACGCTCTA CCCAAAGACGCTGATGCGAACGGTGCTTATTGCATAGCTTTAAAGGGTTTGTATGAG ATCAAACAGATAACAGAAAATTGGAAGGAAGATGGTAAGTTCTCCCGTGACAAGCT TAAAATATCAAATAAGGACTGGTTCGATTTTATACAGAATAAGCGTTATTAAAACGT CCGGCAGCGACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCG GCGCAGGCAGCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAA GGTTATTCCGGGCTAA SEQ ID NO: 55 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA CAATGGAACTAATAACTTCCAGAATTTCATTGGTATCTCCTCTTTACAAAAAACTCT AAGAAACGCCCTAATTCCGACTGAAACTACACAGCAATTCATCGTCAAAAACGGGA TCATTAAGGAGGATGAGTTGAGGGGTGAAAATCGTCAAATTCTTAAAGACATCATG GACGACTACTACAGGGGGTTCATCAGCGAGACGTTATCTAGTATAGACGATATAGA CTGGACTTCACTGTTCGAGAAGATGGAAATCCAATTAAAAAATGGGGACAATAAAG ATACACTTATAAAGGAACAGACAGAGTATAGAAAGGCAATACACAAAAAGTTTGCC AACGACGATCGTTTCAAGAACATGTTTAGTGCTAAATTGATTTCAGATATTCTGCCG GAATTTGTTATTCACAACAATAATTATAGCGCCAGTGAGAAAGAAGAAAAAACGCA GGTTATCAAACTGTTCAGTCGTTTCGCTACATCTTTTAAGGATTACTTTAAAAACCGT GCAAATTGTTTTTCAGCCGACGATATTAGTAGCAGCTCTTGTCACCGTATTGTTAATG ATAATGCGGAGATTTTCTTTTCAAACGCATTGGTCTACAGGAGGATAGTCAAGTCCC TTTCAAATGACGACATTAATAAGATCTCAGGTGACATGAAAGATTCCTTAAAGGAA ATGTCCCTGGAAGAGATCTATTCCTATGAAAAGTACGGTGAGTTCATTACTCAAGAG GGTATAAGCTTTTACAATGACATATGTGGTAAGGTTAATAGCTTTATGAACCTGTAT TGCCAGAAGAACAAAGAAAATAAGAATCTGTATAAGTTGCAAAAGCTACACAAACA AATTTTGTGCATTGCCGATACATCATACGAGGTGCCATACAAATTCGAGAGCGATGA GGAGGTTTATCAGAGCGTGAATGGATTCCTGGACAATATTAGTAGTAAGCATATCGT GGAAAGGCTTAGAAAGATAGGTGACAATTACAATGGCTACAATCTGGATAAAATCT ACATCGTCTCAAAATTCTATGAAAGTGTATCCCAGAAGACGTACCGTGATTGGGAAA CTATCAACACCGCTCTGGAGATACATTACAACAATATACTTCCCGGAAACGGCAAGT CAAAAGCCGACAAAGTCAAAAAAGCGGTCAAGAACGATTTACAAAAGTCTATCACT GAAATTAATGAATTAGTTAGTAATTACAAACTGTGTAGTGATGATAATATTAAGGCA GAGACTTACATACACGAAATTTCACACATTTTAAACAACTTCGAGGCACAGGAACTT AAATATAATCCTGAAATTCACCTGGTTGAAAGTGAATTGAAAGCCAGCGAGCTAAA GAACGTTTTGGACGTAATCATGAACGCATTCCACTGGTGCTCTGTCTTTATGACAGA GGAACTAGTGGATAAGGACAATAATTTTTATGCGGAGCTGGAGGAAATATACGATG AGATATATCCCGTAATATCATTATATAATCTGGTAAGAAACTATGTGACTCAAAAGC CGTATAGCACCAAGAAAATTAAACTTAATTTCGGCATACCCACTTTAGCGGACGGCT GGTCAAAATCCAAAGAGTATAGTAATAATGCCATCATCCTGATGCGTGACAACCTGT ACTATTTAGGTATATTTAACGCCAAAAATAAACCCGACAAAAAGATTATAGAGGGC AACACCTCAGAGAACAAAGGTGATTATAAGAAGATGATTTACAACCTTTTACCCGGT CCTAATAAGATGATTCCCAAAGTCTTTCTATCTAGCAAAACTGGTGTTGAAACATAC AAACCCTCAGCTTATATTTTAGAAGGGTATAAGCAGAATAAGCATATTAAAAGCTCC AAAGATTTCGATATTACCTTTTGCCATGACTTGATAGACTATTTCAAAAATTGTATTG CCATTCACCCTGAATGGAAAAACTTCGGATTTGACTTCTCTGACACATCCACCTACG AAGACATTTCAGGTTTTTACAGGGAAGTCGAGCTACAGGGTTATAAAATTGATTGGA CATACATCAGCGAGAAAGATATTGACCTACTTCAAGAAAAAGGGCAGCTATACCTG TTCCAGATATACAATAAAGACTTCAGTAAAAAAAGCACCGGGAACGATAATCTTCA CACAATGTACTTAAAAAATTTATTTAGTGAAGAGAATCTGAAGGATATAGTGCTGAA GTTAAACGGGGAGGCAGAGATATTTTTTAGAAAATCTAGTATTAAGAATCCGATCAT CCACAAGAAGGGTTCTATCCTTGTTAATAGGACTTATGAGGCAGAAGAAAAAGACC AATTCGGCAACATACAAATTGTCCGTAAAAATATCCCTGAGAACATTTATCAGGAAC TATACAAGTACTTCAATGATAAAAGCGACAAGGAGCTGAGCGACGAGGCTGCTAAG TTAAAGAATGTGGTGGGCCACCATGAGGCAGCAACGAATATTGTGAAGGACTATCG TTATACCTACGATAAATACTTTCTTCATATGCCGATCACCATTAATTTCAAGGCAAAC AAAACTGGCTTCATTAACGATCGTATCTTACAATATATCGCAAAAGAGAAAGACCTT CACGTTATCGGGATCGATAGAGGCGAGCGTAACCTAATTTATGTTTCTGTGATAGAC ACCTGTGGGAACATAGTCGAACAGAAATCATTTAATATTGTTAACGGCTACGATTAT CAGATAAAGTTGAAGCAACAAGAGGGTGCACGTCAAATAGCAAGGAAAGAATGGA AAGAAATAGGCAAGATTAAAGAAATAAAAGAAGGTTATTTATCCCTTGTAATACAC GAAATTAGCAAAATGGTGATTAAATATAATGCGATCATTGCCATGGAGGATCTTTCT TACGGCTTCAAAAAGGGGAGATTCAAAGTCGAGAGGCAGGTGTATCAGAAGTTTGA GACCATGCTAATCAATAAACTAAATTATCTAGTATTCAAAGACATAAGCATCACCGA AAATGGCGGCTTGTTGAAGGGTTATCAATTGACCTACATCCCAGATAAACTAAAAA ACGTAGGGCATCAATGCGGATGTATATTTTACGTTCCAGCCGCATACACTTCCAAAA TCGATCCAACTACGGGTTTTGTGAACATCTTCAAATTCAAAGACTTGACTGTCGATG CTAAGAGGGAGTTTATCAAGAAATTTGACTCCATTAGATACGACAGTGAGAAGAAT CTGTTCTGTTTTACCTTTGATTATAACAACTTTATAACTCAAAACACAGTCATGAGTA AGTCATCTTGGTCAGTGTATACGTATGGTGTGAGGATTAAAAGGAGGTTTGTTAACG GGAGATTTTCCAATGAAAGTGATACAATAGATATAACCAAGGACATGGAAAAGACT CTTGAAATGACCGACATTAACTGGAGAGATGGCCACGACTTACGTCAAGATATAAT CGATTACGAGATAGTGCAACATATCTTTGAGATATTTAGGCTTACTGTCCAAATGCG TAACTCATTAAGTGAGTTGGAGGACAGGGATTACGATAGGCTAATAAGTCCTGTTCT TAACGAAAACAATATATTCTACGATTCAGCAAAGGCGGGAGACGCCCTGCCCAAGG ACGCGGATGCTAACGGCGCATACTGTATTGCCCTGAAAGGCTTGTACGAGATAAAA CAGATCACGGAGAACTGGAAAGAAGATGGAAAATTCAGTCGTGACAAGTTAAAAAT TAGTAACAAAGACTGGTTCGACTTTATTCAGAACAAGAGATATCTGAAACGTCCGGC AGCGACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCA GGCAGCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTA TTCCGGGCTAA SEQ ID NO: 56 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA CAACGGAACCAATAACTTTCAAAACTTTATAGGCATCTCCAGTCTACAGAAGACACT ACGTAACGCTTTGATACCAACTGAGACCACGCAGCAGTTTATCGTCAAGAACGGTAT TATAAAGGAAGACGAGCTAAGGGGGGAAAACCGTCAGATCTTAAAGGACATCATGG ATGACTACTACAGAGGCTTCATAAGTGAGACTTTGTCTAGTATAGACGACATCGACT GGACCAGTTTATTTGAGAAGATGGAAATTCAGTTAAAGAACGGGGACAATAAAGAC ACACTAATTAAAGAGCAGACCGAATACAGAAAAGCTATACACAAAAAGTTTGCCAA CGATGATAGATTCAAAAATATGTTTTCAGCAAAATTGATTTCCGACATATTGCCAGA ATTCGTAATCCATAATAACAATTATTCTGCAAGTGAGAAGGAAGAGAAGACCCAAG TAATCAAGCTGTTTTCCCGTTTTGCTACGAGTTTCAAAGATTATTTCAAGAATAGGGC TAATTGTTTCTCCGCGGACGACATAAGTAGCAGTTCCTGTCACAGGATTGTGAACGA TAATGCTGAGATATTTTTTTCCAATGCCCTAGTGTATAGGAGAATAGTTAAAAGCTT AAGCAACGACGATATCAATAAAATTTCAGGGGACATGAAGGACAGCTTAAAGGAAA TGAGTTTGGAGGAGATTTACAGTTATGAAAAATACGGAGAGTTTATAACTCAGGAA GGCATCTCTTTCTATAATGATATCTGTGGGAAGGTAAACTCCTTCATGAATTTATATT GCCAGAAGAATAAGGAAAACAAAAATCTTTACAAGCTTCAAAAGTTACATAAGCAG ATCTTATGTATTGCCGACACGAGTTATGAAGTGCCTTATAAATTCGAGAGTGATGAG GAAGTGTATCAGTCTGTTAACGGATTCCTAGATAATATAAGTTCCAAACATATAGTC GAGAGGCTGAGGAAGATTGGCGATAACTATAATGGATATAATCTTGACAAAATCTA TATAGTCTCTAAATTTTATGAAAGCGTCAGCCAGAAGACATATAGAGATTGGGAAA CTATAAACACAGCCCTTGAAATACATTACAATAACATCCTACCCGGCAATGGTAAGT CTAAGGCAGACAAAGTTAAAAAAGCAGTAAAGAATGACTTACAGAAGTCAATCACG GAGATAAATGAGTTGGTCAGTAACTACAAATTATGCTCCGACGATAATATTAAGGCC GAAACATATATACACGAGATAAGTCATATATTAAACAATTTCGAAGCCCAGGAGTT AAAATATAACCCTGAAATTCATCTGGTCGAAAGTGAGTTAAAGGCCAGTGAGTTAA AGAATGTACTTGACGTAATTATGAATGCTTTTCATTGGTGCTCCGTGTTCATGACCGA GGAGTTAGTAGATAAAGACAATAACTTTTACGCCGAACTTGAAGAGATATACGACG AGATTTATCCGGTAATCAGCTTGTACAACTTAGTTAGAAATTATGTAACACAGAAGC CTTACTCTACTAAAAAAATAAAACTGAACTTTGGTATCCCAACTCTTGCAGATGGTT GGAGTAAAAGCAAGGAATATAGCAACAATGCGATCATCTTGATGAGAGACAACTTG TACTATTTGGGAATCTTCAACGCGAAAAATAAACCCGACAAAAAAATCATCGAAGG GAATACCTCTGAGAATAAAGGTGACTATAAGAAAATGATTTACAATCTACTTCCTGG TCCTAATAAAATGATCCCGAAAGTGTTTCTTAGTTCTAAGACTGGTGTCGAGACGTA CAAACCTAGCGCGTACATCTTAGAAGGGTACAAGCAGAATAAACACATCAAATCAA GCAAAGACTTCGATATTACTTTTTGCCATGACTTGATAGACTACTTTAAAAACTGCA TAGCAATCCACCCGGAGTGGAAAAACTTTGGCTTTGATTTCTCTGACACCTCTACAT ATGAGGACATATCTGGTTTTTACCGTGAGGTTGAATTGCAGGGATACAAAATTGACT GGACTTACATATCTGAAAAAGATATCGATCTATTGCAGGAGAAAGGCCAGCTTTACC TTTTCCAGATCTATAATAAGGACTTCTCTAAGAAGTCTACAGGGAATGATAATTTGC ACACTATGTACTTAAAAAATCTGTTTTCCGAGGAAAACTTGAAAGACATTGTTTTAA AGTTGAACGGAGAAGCTGAAATATTTTTCAGAAAGAGCTCCATAAAAAACCCGATC ATTCATAAGAAGGGATCTATCCTGGTTAACAGAACGTACGAAGCGGAAGAAAAAGA CCAATTCGGAAACATTCAAATTGTTAGAAAGAATATCCCTGAGAACATCTACCAGG AGTTATATAAGTATTTTAATGATAAGTCAGATAAGGAACTATCTGACGAAGCGGCG AAGCTTAAAAATGTTGTAGGACACCATGAGGCTGCTACAAATATAGTCAAGGACTA CCGTTATACCTACGATAAGTACTTTCTACACATGCCCATTACCATCAATTTTAAAGCT AATAAAACGGGTTTTATCAACGATCGTATCCTACAATATATTGCGAAAGAGAAGGA TTTGCATGTCATTGGCATTGATAGAGGTGAGAGGAACCTAATATACGTATCCGTGAT TGATACGTGCGGGAACATAGTTGAACAGAAATCATTTAATATAGTTAATGGGTACG ACTATCAGATTAAGCTAAAGCAACAAGAAGGCGCCAGGCAAATTGCCCGTAAAGAA TGGAAAGAGATCGGGAAGATCAAGGAAATAAAAGAAGGATACCTTTCCCTGGTCAT CCATGAAATTAGCAAAATGGTGATTAAGTACAATGCCATAATCGCGATGGAGGACT TAAGCTACGGGTTCAAAAAGGGGAGGTTTAAGGTGGAGAGGCAAGTGTACCAGAAA TTTGAGACCATGCTAATCAACAAACTGAACTACCTAGTTTTTAAGGACATTTCAATT ACAGAGAATGGAGGACTTTTAAAGGGTTACCAACTAACGTATATACCAGATAAGTT GAAAAATGTCGGTCACCAGTGTGGCTGCATCTTTTACGTTCCCGCCGCTTATACATCT AAAATTGATCCAACCACAGGCTTTGTAAATATCTTTAAATTCAAAGATTTAACTGTG GATGCAAAAAGAGAGTTTATCAAGAAATTCGATAGCATTCGTTATGATAGCGAGAA GAACCTGTTCTGCTTTACTTTCGACTATAACAACTTTATAACTCAAAACACCGTGATG TCAAAAAGCTCATGGTCAGTCTACACCTATGGTGTAAGGATTAAAAGGCGTTTCGTG AATGGGAGATTCTCCAATGAAAGTGACACGATCGACATAACAAAGGACATGGAGAA GACACTAGAGATGACTGATATTAATTGGAGAGACGGACACGATCTGCGTCAAGATA TAATTGATTATGAGATAGTACAGCACATATTTGAGATCTTCCGTTTGACTGTCCAAA TGCGTAATTCCCTTTCTGAGCTGGAAGATAGGGACTATGATAGATTAATATCCCCTG TACTAAATGAGAACAACATTTTCTATGATAGTGCAAAAGCCGGGGATGCATTGCCG AAAGACGCTGACGCTAATGGGGCGTACTGTATAGCTTTAAAGGGGCTTTACGAAAT AAAGCAGATAACCGAAAACTGGAAGGAAGATGGCAAATTCTCAAGGGACAAACTT AAGATCTCTAACAAGGATTGGTTCGATTTTATACAAAACAAACGTTATTTGAAACGT CCGGCAGCGACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCG GCGCAGGCAGCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAA GGTTATTCCGGGCTAA SEQ ID NO: 57 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA TAATGGTACAAACAACTTTCAGAATTTCATTGGGATCTCTAGCTTACAGAAGACCCT GAGGAATGCGTTGATTCCAACTGAAACAACCCAGCAATTCATCGTGAAAAATGGGA TAATCAAAGAGGATGAGTTAAGGGGTGAAAACCGTCAAATATTGAAGGATATTATG GACGACTACTACCGTGGATTCATCTCAGAGACGTTGAGCAGCATTGACGACATAGA CTGGACTAGCCTTTTCGAGAAGATGGAAATTCAGTTAAAGAACGGAGATAACAAAG ATACACTAATCAAGGAACAGACAGAATACAGAAAAGCAATTCATAAGAAATTCGCT AATGACGATCGTTTTAAAAACATGTTCTCTGCAAAATTAATTAGCGACATTCTGCCG GAATTCGTTATACATAATAATAACTACAGTGCTTCTGAAAAGGAAGAGAAAACTCA GGTAATAAAACTGTTCTCTCGTTTTGCCACATCCTTCAAAGACTACTTTAAAAATAG AGCGAACTGCTTTAGCGCCGACGATATTAGTTCTTCCTCATGCCACAGGATTGTCAA CGATAATGCAGAGATATTCTTTTCTAACGCACTAGTCTACAGAAGGATTGTAAAGTC TTTGTCAAATGATGACATAAACAAGATTAGTGGAGATATGAAAGACTCTCTAAAGG AAATGAGCCTTGAGGAGATATACTCTTATGAAAAGTACGGTGAGTTTATTACCCAAG AAGGCATTAGTTTCTATAATGACATTTGTGGAAAAGTTAACAGTTTTATGAATCTAT ACTGTCAAAAAAATAAGGAGAATAAAAATCTTTATAAGTTGCAAAAACTGCATAAG CAGATATTATGTATAGCAGACACGAGCTATGAGGTACCGTACAAGTTCGAGAGCGA TGAGGAAGTCTACCAATCTGTCAACGGATTTTTGGACAACATTTCTTCAAAACATAT TGTGGAGAGGCTTAGGAAAATAGGCGACAATTATAATGGATATAACTTAGATAAGA TATATATTGTTTCCAAATTCTACGAATCTGTAAGCCAGAAGACATACAGAGATTGGG AAACGATAAACACAGCCCTTGAAATTCACTATAACAACATACTACCTGGAAACGGC AAATCAAAGGCCGACAAAGTTAAGAAGGCCGTAAAGAATGATTTACAGAAGAGCAT AACGGAGATCAATGAGCTGGTGTCTAACTATAAATTGTGTAGCGATGACAACATAA AAGCCGAGACTTACATTCACGAAATTTCACACATACTTAACAACTTTGAAGCTCAGG AATTAAAGTATAATCCCGAAATACACCTTGTGGAGTCCGAACTAAAGGCTAGTGAG CTTAAGAACGTCCTAGACGTAATTATGAATGCCTTCCACTGGTGTAGTGTTTTTATGA CCGAGGAACTTGTTGACAAAGATAATAATTTTTATGCAGAACTAGAAGAGATATAC GATGAAATATACCCGGTGATCAGTTTGTACAATCTTGTCAGGAACTATGTGACACAA AAGCCCTATTCAACAAAGAAAATAAAACTTAATTTCGGAATTCCTACGTTAGCTGAT GGCTGGTCTAAATCCAAGGAATACAGCAACAACGCTATAATTCTGATGAGAGATAA CTTGTACTATCTAGGCATCTTCAATGCCAAAAATAAGCCTGATAAGAAGATTATAGA GGGCAACACTTCAGAGAACAAGGGCGACTACAAGAAAATGATCTATAACCTATTGC CTGGCCCAAACAAGATGATTCCGAAGGTCTTCCTATCATCCAAGACCGGCGTTGAGA CATACAAGCCATCAGCGTATATTTTAGAGGGGTACAAACAAAACAAGCACATAAAG TCTAGTAAAGACTTCGATATAACATTTTGTCATGACTTAATTGACTACTTTAAGAATT GCATCGCTATACACCCGGAATGGAAGAATTTCGGCTTCGACTTCTCTGATACATCTA CCTACGAGGACATTAGCGGGTTTTACCGTGAAGTCGAATTACAAGGGTATAAGATA GATTGGACGTACATCTCTGAGAAAGACATAGACTTGCTTCAGGAAAAGGGCCAGTT GTATCTATTCCAAATATACAATAAGGATTTTTCCAAGAAATCTACGGGTAATGACAA TCTTCACACAATGTATCTTAAGAACCTTTTCTCAGAAGAGAACCTGAAGGACATTGT CTTAAAACTAAATGGCGAAGCTGAGATTTTTTTCAGGAAGTCTTCAATTAAGAACCC GATAATCCACAAGAAGGGGAGTATTCTTGTGAATAGAACTTACGAGGCCGAAGAAA AAGACCAATTTGGTAACATCCAGATAGTCAGAAAGAACATTCCAGAGAACATCTAC CAAGAGCTATACAAATATTTCAACGACAAGTCCGATAAGGAACTGTCCGATGAGGC AGCCAAGTTGAAGAATGTCGTGGGTCATCATGAAGCTGCTACTAACATTGTCAAGG ACTATCGTTATACTTACGACAAGTATTTCCTACACATGCCGATAACAATTAATTTCA AGGCTAACAAAACAGGCTTTATCAACGATCGTATCTTGCAGTACATAGCTAAGGAA AAGGATTTGCATGTGATTGGCATTGATAGAGGGGAGCGTAACTTGATATATGTGTCT GTCATAGACACGTGTGGCAACATCGTCGAACAGAAATCATTCAACATAGTAAACGG CTACGATTACCAAATTAAGCTGAAACAGCAAGAGGGTGCACGTCAAATTGCGCGTA AAGAGTGGAAAGAAATTGGTAAAATCAAGGAAATTAAAGAAGGCTACTTGTCTCTT GTTATACATGAAATTTCCAAGATGGTTATAAAGTATAACGCGATAATTGCTATGGAA GACTTATCATACGGGTTTAAAAAGGGGAGGTTCAAGGTAGAGAGGCAGGTCTATCA AAAGTTCGAGACGATGTTGATTAATAAACTAAACTATCTAGTGTTCAAAGATATCAG CATTACGGAGAACGGGGGGCTACTGAAAGGATATCAACTAACGTACATTCCCGATA AGTTAAAGAACGTTGGTCATCAATGTGGTTGCATCTTCTACGTGCCTGCTGCCTATA CGTCCAAAATAGATCCAACTACTGGATTTGTTAACATCTTTAAATTCAAAGATTTAA CCGTAGACGCCAAAAGGGAATTTATAAAAAAATTTGACAGCATCCGTTACGATAGC GAAAAGAATCTGTTCTGTTTTACTTTCGACTACAATAATTTCATCACGCAAAATACG GTAATGTCTAAGTCAAGTTGGAGCGTCTACACGTATGGAGTCAGGATCAAGAGGCG TTTCGTAAATGGAAGATTCTCTAATGAGTCAGATACTATAGACATCACGAAAGATAT GGAGAAAACCTTGGAGATGACGGATATTAACTGGCGTGATGGACACGATTTAAGAC AGGACATTATTGACTATGAGATTGTGCAACACATCTTCGAAATATTCCGTCTAACAG TCCAAATGAGGAATAGCCTAAGTGAATTGGAGGACCGTGATTACGATAGGCTTATA AGTCCTGTCCTTAACGAAAACAATATTTTCTATGATAGTGCTAAGGCGGGGGACGCA CTGCCTAAAGACGCAGATGCTAACGGGGCATACTGCATTGCGTTAAAGGGTCTGTAC GAAATCAAGCAGATTACGGAAAACTGGAAAGAGGATGGCAAGTTTAGCAGAGATA AGTTGAAGATAAGTAACAAAGATTGGTTTGACTTTATTCAGAATAAAAGGTATTTAA AACGTCCGGCAGCGACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGG TAGCGGCGCAGGCAGCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAA CGTAAGGTTATTCCGGGCTAA SEQ ID NO: 58 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA TAACGGCACTAATAATTTCCAGAATTTCATCGGCATTAGCAGCTTACAAAAGACGTT GAGGAATGCCTTAATACCCACAGAAACTACTCAACAATTTATAGTGAAGAATGGGA TAATTAAGGAAGACGAGTTGAGAGGTGAAAATAGGCAAATCTTGAAAGACATTATG GATGACTACTACAGGGGCTTCATTAGTGAAACGTTGTCTTCAATAGATGACATTGAT TGGACTTCTTTGTTTGAGAAGATGGAAATACAGTTAAAGAACGGCGACAATAAGGA TACACTTATCAAAGAGCAAACAGAATATAGAAAAGCAATTCACAAAAAGTTTGCTA ACGATGATAGGTTCAAGAACATGTTTAGCGCTAAACTAATATCAGACATCCTTCCCG AGTTCGTTATTCATAACAATAACTATAGTGCAAGTGAAAAAGAGGAGAAGACACAG GTGATTAAGCTGTTCTCCAGATTCGCGACTTCTTTCAAAGATTACTTCAAAAACAGA GCCAACTGTTTTTCAGCTGACGATATCTCTAGTAGTAGTTGTCACCGTATAGTGAAC GATAACGCTGAGATCTTCTTTAGCAATGCATTAGTGTATAGAAGGATAGTTAAGTCT CTAAGCAATGATGATATCAATAAAATTTCCGGAGACATGAAGGACTCCCTAAAGGA AATGTCCTTAGAAGAGATCTACTCATATGAGAAATACGGGGAATTTATTACGCAGG AAGGGATCTCCTTTTACAATGACATATGCGGGAAGGTCAACTCTTTCATGAACTTAT ACTGCCAAAAGAACAAGGAGAACAAGAATTTATATAAACTTCAGAAACTTCACAAA CAAATACTGTGCATAGCCGATACCTCATATGAGGTTCCTTACAAATTTGAATCAGAT GAAGAGGTATACCAATCCGTTAACGGCTTTCTTGACAATATTAGCTCAAAGCACATC GTGGAGAGGTTGAGAAAGATTGGTGATAATTATAATGGCTACAATCTAGATAAGAT ATATATTGTTAGCAAGTTCTACGAGTCTGTGTCCCAAAAAACATATAGGGATTGGGA GACAATTAATACTGCTCTAGAAATCCATTACAACAACATCCTTCCTGGAAATGGCAA GAGTAAGGCCGACAAAGTCAAGAAAGCAGTGAAAAATGATCTGCAAAAATCAATTA CTGAGATAAACGAGCTAGTATCTAATTACAAGCTTTGTAGCGACGATAACATTAAGG CAGAAACGTACATACACGAGATTAGTCACATCTTAAATAATTTTGAAGCCCAAGAA CTGAAATATAACCCTGAGATACACCTTGTTGAATCCGAGTTAAAGGCGTCTGAACTA AAAAACGTGTTAGACGTTATTATGAATGCCTTCCACTGGTGTAGCGTCTTTATGACT GAGGAGTTGGTTGATAAGGATAATAACTTTTACGCTGAATTGGAAGAAATTTATGAC GAAATCTATCCTGTTATTTCTCTATATAATTTGGTGAGAAATTACGTAACGCAAAAG CCCTATAGTACGAAAAAAATAAAACTAAATTTCGGGATCCCTACCCTAGCCGACGGT TGGTCTAAATCCAAGGAGTACTCAAACAATGCAATAATATTGATGAGGGACAACCT GTACTACCTAGGCATATTTAATGCCAAAAATAAGCCCGATAAAAAGATTATAGAAG GGAACACGTCAGAAAATAAAGGAGACTATAAGAAAATGATCTACAACCTTTTGCCC GGCCCCAATAAAATGATCCCGAAGGTCTTCCTAAGTAGCAAGACTGGCGTAGAGAC CTACAAACCATCTGCATACATTTTGGAGGGGTACAAGCAAAACAAGCACATAAAGA GTAGTAAGGATTTTGACATTACATTCTGCCATGACTTAATTGACTACTTTAAAAATTG CATCGCAATTCACCCTGAATGGAAAAATTTTGGATTTGATTTCTCTGATACTTCAACA TATGAGGATATTTCAGGGTTCTACAGGGAGGTCGAACTACAGGGTTACAAAATAGA CTGGACGTATATTTCTGAGAAAGATATAGATTTGCTTCAGGAAAAGGGTCAGCTATA TCTGTTCCAGATATATAATAAGGACTTCTCCAAAAAGAGTACCGGAAATGATAATCT GCACACAATGTACTTAAAAAACTTGTTCTCTGAGGAGAATCTAAAAGACATCGTACT AAAACTTAACGGGGAGGCCGAAATTTTTTTTAGGAAGTCCAGCATCAAGAACCCGA TTATTCATAAAAAAGGTAGCATTTTGGTGAACCGTACTTATGAGGCGGAAGAAAAA GACCAATTCGGTAATATTCAAATCGTTAGAAAGAACATCCCTGAGAACATTTATCAG GAACTATACAAATACTTTAACGACAAATCAGATAAGGAGCTTTCTGATGAGGCAGC TAAATTGAAAAATGTAGTGGGACATCACGAAGCAGCCACTAACATAGTGAAGGACT ACAGATACACATACGATAAGTACTTCCTGCACATGCCTATTACAATTAACTTTAAAG CAAATAAAACAGGGTTTATTAACGACAGAATCTTACAGTATATTGCCAAAGAAAAG GATCTGCATGTGATAGGAATAGACAGAGGAGAAAGAAACCTGATATACGTCTCCGT GATTGATACATGTGGGAACATAGTAGAACAGAAGTCCTTTAACATTGTTAATGGGTA CGATTATCAAATTAAATTAAAACAACAAGAAGGAGCACGTCAAATAGCTAGGAAAG AATGGAAAGAGATAGGAAAAATTAAGGAAATTAAGGAGGGTTACCTGTCCCTTGTA ATTCATGAAATATCCAAAATGGTAATTAAATATAACGCGATCATCGCGATGGAAGA TCTAAGCTACGGGTTCAAAAAAGGCAGGTTTAAGGTGGAGAGGCAAGTTTACCAAA AGTTCGAGACAATGTTGATTAATAAGTTAAACTACTTAGTTTTCAAAGATATCTCCA TAACCGAGAATGGCGGGCTTTTAAAAGGGTACCAACTAACATATATCCCGGATAAA TTGAAGAACGTTGGACACCAGTGTGGCTGCATATTTTATGTACCCGCTGCGTATACT TCTAAAATTGACCCGACCACCGGGTTTGTAAACATATTCAAGTTTAAGGACCTAACA GTTGACGCCAAACGTGAGTTCATCAAGAAGTTCGATAGTATAAGGTATGACTCTGAG AAGAACCTTTTCTGCTTCACGTTTGACTATAATAATTTCATCACCCAAAATACAGTTA TGTCAAAAAGCTCTTGGTCAGTATATACGTATGGCGTAAGGATTAAGCGTAGGTTCG TGAACGGTAGATTTTCCAACGAGTCAGATACTATTGATATTACCAAGGATATGGAGA AGACATTAGAAATGACAGATATAAATTGGAGGGATGGGCACGATCTAAGGCAAGAT ATCATTGATTACGAAATTGTTCAGCACATATTCGAGATATTCCGTCTTACAGTACAA ATGCGTAACAGCTTGTCTGAGTTGGAAGATCGTGACTATGACAGGTTGATATCACCG GTCTTGAACGAGAACAATATATTCTACGACAGCGCTAAGGCGGGAGACGCTCTGCC TAAAGACGCAGATGCCAATGGGGCGTACTGCATTGCCTTAAAAGGCTTATACGAGA TTAAACAGATCACAGAGAACTGGAAAGAGGACGGCAAGTTTTCTAGAGATAAATTG AAAATCTCAAACAAAGACTGGTTCGATTTCATCCAAAACAAAAGATACCTTAAACG TCCGGCAGCGACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGC GGCGCAGGCAGCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTA AGGTTATTCCGGGCTAA SEQ ID NO: 59 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA CAATGGAACTAACAACTTCCAGAACTTTATCGGCATCTCTTCCCTCCAAAAGACACT GAGAAATGCACTGATCCCAACCGAAACGACTCAACAATTTATTGTTAAGAACGGCA TCATAAAAGAAGACGAGCTTCGCGGCGAGAACCGCCAGATACTTAAGGATATTATG GACGATTATTACCGAGGCTTTATCAGCGAAACTCTTAGCTCTATTGATGATATCGAC TGGACCTCCCTCTTCGAAAAAATGGAGATACAGCTCAAGAACGGCGATAATAAAGA CACCTTGATAAAGGAACAGACTGAGTACAGGAAAGCGATCCACAAGAAATTCGCGA ACGACGACAGGTTTAAAAACATGTTCTCTGCAAAATTGATATCCGACATCTTGCCGG AATTTGTGATACACAACAATAACTATAGCGCTTCAGAGAAAGAAGAGAAGACCCAA GTAATCAAGTTGTTCAGCCGCTTCGCAACGTCTTTTAAAGATTACTTTAAGAACCGG GCCAATTGTTTCTCCGCGGATGATATTAGCTCATCAAGTTGCCATCGAATTGTCAAT GATAATGCGGAGATCTTCTTCAGCAATGCGCTGGTCTACAGACGAATCGTAAAAAGT CTTTCAAATGACGACATCAATAAGATTAGTGGAGATATGAAGGATTCCCTTAAGGA AATGAGTCTTGAAGAAATATACTCATACGAAAAGTACGGGGAATTTATTACCCAGG AGGGGATCTCCTTCTATAACGACATCTGTGGAAAAGTAAACTCATTCATGAACCTGT ACTGTCAGAAAAACAAAGAAAACAAAAATCTGTATAAACTCCAAAAATTGCACAAG CAAATATTGTGTATAGCGGACACATCATACGAGGTTCCATATAAGTTCGAAAGTGAT GAAGAAGTCTACCAATCAGTGAATGGGTTTCTGGACAACATTAGTTCCAAGCACATA GTTGAACGACTGCGAAAGATTGGTGACAATTACAACGGCTATAATTTGGACAAGAT TTATATAGTTAGCAAATTTTATGAATCCGTATCACAAAAGACTTATAGAGACTGGGA AACAATCAACACGGCACTTGAGATCCATTATAACAATATTCTTCCAGGGAACGGCA AAAGCAAGGCTGATAAGGTAAAAAAGGCCGTTAAGAATGATCTTCAAAAATCCATA ACGGAGATCAACGAACTTGTAAGTAACTACAAATTGTGCTCTGACGACAATATAAA GGCTGAAACGTATATTCACGAGATTAGCCATATCCTGAATAACTTTGAGGCCCAAGA ACTCAAGTATAACCCGGAAATACATTTGGTAGAAAGCGAGCTTAAAGCGAGTGAGC TGAAAAACGTCCTCGATGTGATCATGAATGCTTTCCACTGGTGTAGTGTCTTTATGA CTGAGGAGTTGGTTGATAAAGACAATAATTTCTACGCTGAACTGGAAGAAATTTACG ACGAAATCTATCCAGTGATCTCCCTCTATAACCTCGTTCGAAACTACGTGACGCAGA AACCTTATTCTACAAAGAAAATTAAGTTGAACTTCGGCATTCCTACACTTGCTGACG GATGGTCCAAATCCAAAGAGTACTCAAACAACGCAATCATCCTCATGCGGGATAAC CTTTATTATTTGGGCATTTTCAACGCCAAAAACAAACCTGATAAAAAGATAATTGAA GGCAATACGAGTGAGAACAAGGGCGACTACAAAAAAATGATATATAACTTGTTGCC AGGCCCCAACAAGATGATTCCTAAAGTTTTTCTGTCTTCTAAGACTGGAGTTGAAAC TTACAAACCCTCCGCCTACATTCTTGAAGGGTATAAACAGAATAAGCACATAAAGTC CTCAAAGGATTTCGACATTACGTTTTGCCATGACCTCATCGACTATTTCAAGAACTGT ATCGCCATACATCCGGAGTGGAAGAATTTTGGATTTGATTTCTCCGACACATCTACC TATGAAGACATAAGCGGTTTCTACCGGGAGGTCGAGCTTCAGGGCTATAAGATAGA TTGGACATACATTAGTGAAAAAGATATCGATCTTCTGCAAGAAAAGGGACAACTTT ACCTTTTTCAGATTTATAATAAAGACTTTTCAAAAAAGTCCACAGGGAACGATAATC TGCACACCATGTATCTCAAGAATCTGTTTAGTGAAGAAAACCTTAAAGACATAGTTT TGAAGCTTAACGGAGAGGCTGAGATTTTTTTTAGAAAGTCCTCAATTAAAAACCCTA TAATACACAAGAAAGGCTCTATTCTTGTTAACAGGACATATGAAGCCGAGGAGAAA GATCAGTTTGGCAATATCCAGATTGTTCGCAAGAATATCCCGGAAAATATATATCAG GAGCTGTATAAATACTTTAACGACAAGAGCGACAAGGAGCTGAGTGACGAGGCCGC GAAGCTTAAGAATGTAGTAGGTCACCACGAAGCAGCCACCAATATCGTCAAAGACT ATAGGTACACGTACGACAAGTACTTTTTGCACATGCCTATAACTATAAACTTCAAAG CTAATAAAACTGGGTTTATTAATGACAGGATTCTCCAATACATCGCTAAAGAGAAGG ATCTGCATGTAATTGGCATAGACAGAGGTGAGAGAAACTTGATATATGTCAGCGTA ATAGACACATGTGGCAATATCGTGGAACAGAAGTCTTTTAACATCGTCAATGGTTAC GACTACCAAATTAAGTTGAAACAGCAGGAAGGCGCACGACAGATCGCACGAAAGG AATGGAAAGAGATAGGCAAAATAAAAGAAATAAAGGAGGGCTATCTCAGTCTCGTT ATACACGAAATTTCAAAAATGGTTATTAAGTACAATGCAATCATAGCGATGGAGGA TCTCAGTTATGGGTTCAAAAAGGGTCGGTTTAAAGTTGAGCGCCAAGTGTACCAAAA GTTCGAGACAATGCTGATTAACAAGCTGAACTACCTCGTCTTCAAAGATATAAGTAT TACGGAGAACGGTGGCCTTCTTAAAGGCTATCAACTTACTTACATCCCGGACAAGCT CAAAAACGTAGGGCACCAATGCGGGTGTATTTTCTATGTGCCTGCGGCATATACGTC AAAGATTGACCCAACCACAGGATTCGTAAACATATTCAAGTTTAAGGACCTCACCGT TGATGCGAAAAGGGAGTTCATTAAAAAATTTGATTCTATTCGATATGATAGTGAGAA AAATCTCTTTTGTTTCACATTTGACTATAATAATTTTATTACTCAGAATACTGTCATG AGCAAGTCATCTTGGTCAGTGTACACATACGGGGTGCGGATCAAACGCAGGTTCGTC AATGGTCGCTTCTCAAACGAATCAGACACCATTGACATCACAAAGGACATGGAAAA AACCCTTGAGATGACCGACATTAATTGGCGCGATGGTCATGATCTGCGGCAAGACAT CATAGACTACGAAATCGTCCAACACATCTTTGAGATCTTTCGCTTGACGGTCCAAAT GCGGAACTCCCTGTCCGAGCTCGAGGATAGAGATTATGATCGGCTGATATCTCCCGT GCTTAATGAAAATAACATCTTCTACGACTCCGCCAAGGCGGGTGATGCCCTGCCGAA GGATGCGGATGCTAATGGCGCTTATTGCATTGCTCTTAAGGGGCTCTATGAGATAAA GCAGATCACGGAAAACTGGAAAGAAGACGGTAAGTTTAGTAGAGACAAGCTGAAG ATCTCAAATAAAGACTGGTTTGATTTCATACAGAACAAGCGGTACCTGAAACGTCCG GCAGCGACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCG CAGGCAGCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGT TATTCCGGGCTAA SEQ ID NO: 60 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA CAATGGCACTAACAATTTTCAGAATTTCATCGGCATTTCAAGTCTGCAAAAAACTCT GAGGAATGCTTTGATCCCTACTGAAACCACTCAGCAATTTATAGTCAAGAACGGTAT AATTAAAGAAGATGAACTCAGGGGTGAAAATAGACAAATACTCAAGGACATTATGG ATGACTATTATAGAGGCTTCATCTCAGAGACTCTCTCATCAATAGATGATATCGATT GGACTAGCCTTTTCGAGAAAATGGAGATTCAGTTGAAAAATGGTGATAACAAAGAT ACGTTGATAAAGGAACAGACCGAGTACAGGAAAGCCATTCATAAGAAATTTGCTAA TGACGATAGATTTAAGAATATGTTTAGTGCAAAACTGATTAGTGACATTCTGCCGGA GTTCGTTATCCATAATAATAACTACTCTGCATCCGAAAAGGAGGAAAAGACGCAAG TTATTAAACTGTTCAGCCGCTTCGCCACAAGCTTCAAGGACTACTTCAAAAATAGAG CCAACTGCTTTTCTGCCGACGATATATCATCATCTTCATGCCATCGGATCGTTAACGA TAACGCCGAGATATTCTTCAGCAACGCCCTTGTATATCGAAGAATAGTCAAAAGTCT GAGTAATGATGATATTAATAAAATTAGCGGTGATATGAAAGACTCCCTGAAGGAAA TGTCACTGGAGGAAATTTATAGTTACGAAAAGTACGGCGAATTCATTACTCAAGAA GGCATATCCTTCTATAACGACATTTGCGGAAAGGTCAACTCATTCATGAACCTTTAT TGCCAGAAGAATAAGGAGAATAAAAATCTTTACAAATTGCAAAAACTTCACAAACA AATTCTTTGCATCGCGGATACGTCCTACGAAGTTCCTTACAAATTTGAATCCGATGA GGAAGTGTATCAGAGTGTCAATGGATTTTTGGATAATATCTCTTCAAAACATATTGT GGAGAGATTGCGCAAAATAGGTGATAACTACAATGGCTACAACCTGGACAAGATTT ATATTGTTAGCAAGTTCTATGAAAGTGTCAGTCAAAAGACCTACAGAGATTGGGAG ACAATCAACACGGCGCTCGAAATACACTACAATAACATCCTCCCCGGCAATGGGAA GAGTAAAGCCGATAAGGTTAAAAAAGCTGTTAAGAACGACCTCCAGAAATCCATCA CGGAAATAAACGAGCTGGTTTCCAACTATAAGCTGTGTAGCGATGATAATATTAAG GCTGAGACATATATACATGAGATCAGCCACATTCTCAACAATTTCGAGGCACAGGA ACTCAAATACAATCCCGAGATTCACTTGGTGGAAAGTGAGTTGAAGGCGTCAGAGC TTAAGAATGTACTTGACGTAATAATGAATGCTTTTCATTGGTGCTCCGTGTTCATGAC TGAGGAACTCGTGGATAAGGATAATAACTTTTATGCGGAGTTGGAAGAGATATACG ATGAAATATACCCGGTTATCTCACTGTATAATCTGGTCAGAAATTACGTGACCCAAA AGCCTTATAGTACAAAAAAAATAAAGTTGAACTTCGGTATTCCGACATTGGCAGATG GTTGGTCCAAAAGCAAAGAATACTCTAATAACGCCATTATATTGATGCGAGACAATT TGTATTACCTTGGGATCTTTAACGCGAAAAACAAACCGGATAAGAAGATCATCGAA GGTAATACATCTGAGAATAAGGGGGATTACAAGAAGATGATTTATAATCTGTTGCC GGGGCCAAACAAGATGATTCCGAAGGTCTTTCTGTCATCTAAGACAGGAGTAGAGA CCTACAAACCTTCTGCGTACATTTTGGAAGGCTACAAACAGAACAAGCATATAAAAT CTAGCAAGGACTTTGATATCACGTTTTGTCATGATCTGATAGATTATTTCAAAAACT GCATCGCTATACATCCTGAGTGGAAGAATTTCGGCTTTGACTTTTCTGACACCAGCA CATACGAAGACATCTCAGGTTTCTACCGGGAAGTCGAGCTCCAGGGGTACAAGATT GACTGGACATATATAAGTGAAAAAGACATCGACCTCCTCCAAGAGAAGGGCCAACT TTACCTGTTCCAGATCTATAACAAAGACTTTTCTAAAAAGTCCACGGGTAACGACAA CTTGCACACTATGTATCTGAAAAACTTGTTCTCTGAAGAGAACCTCAAGGACATCGT CCTGAAGCTTAACGGGGAGGCGGAGATCTTCTTTAGAAAGTCCTCTATCAAAAATCC CATTATCCATAAAAAGGGCTCTATACTCGTTAATAGGACATATGAAGCGGAGGAAA AAGATCAATTTGGGAACATCCAGATCGTCCGGAAAAATATACCTGAGAATATCTATC AAGAGCTGTACAAGTATTTTAATGATAAGTCAGACAAAGAGCTCAGTGATGAGGCG GCAAAGCTCAAGAACGTGGTGGGGCATCATGAAGCTGCGACGAACATTGTCAAAGA TTATAGATACACTTACGATAAATACTTCCTCCACATGCCGATAACGATTAACTTCAA AGCCAATAAGACGGGGTTTATAAATGATCGGATCCTTCAGTACATTGCGAAAGAGA AAGACCTCCATGTGATCGGAATTGACCGAGGAGAAAGGAATCTGATTTACGTGTCC GTGATTGATACTTGCGGGAATATAGTCGAGCAAAAGAGTTTCAACATAGTCAACGG GTATGACTATCAGATAAAGCTCAAACAGCAGGAAGGTGCGAGGCAAATTGCGCGCA AAGAGTGGAAGGAGATAGGCAAGATTAAAGAAATCAAGGAAGGTTATCTCAGCTTG GTGATCCATGAAATATCTAAGATGGTTATAAAGTACAATGCCATAATAGCCATGGA GGATCTTTCCTACGGGTTTAAGAAGGGCCGATTTAAAGTGGAGCGACAAGTTTACCA GAAGTTCGAAACCATGTTGATTAACAAACTTAACTATTTGGTGTTCAAGGATATAAG TATAACCGAAAACGGCGGTTTGCTTAAGGGTTATCAGCTCACGTATATTCCTGATAA ACTTAAAAACGTTGGACACCAGTGTGGATGTATCTTCTACGTGCCAGCCGCTTACAC TAGTAAGATAGATCCTACCACGGGGTTTGTGAATATTTTTAAGTTTAAAGACTTGAC AGTCGACGCCAAAAGGGAATTTATAAAAAAGTTTGATTCTATCCGCTACGATAGTGA AAAAAATCTCTTTTGCTTTACTTTCGACTATAACAACTTCATTACGCAGAACACTGTC ATGAGTAAGTCCAGCTGGAGCGTCTACACATATGGCGTCCGAATTAAACGACGATTT GTAAACGGGCGGTTTTCAAACGAATCTGACACGATAGACATTACCAAGGATATGGA GAAGACACTTGAGATGACCGACATAAACTGGCGGGACGGTCACGATCTTCGGCAGG ACATAATTGATTACGAAATCGTCCAGCATATATTCGAAATATTTCGACTTACAGTGC AAATGCGGAACAGTCTCTCTGAACTGGAAGATCGCGATTATGACCGGTTGATTTCTC CGGTCCTCAATGAAAATAACATATTTTATGATAGTGCTAAGGCAGGTGATGCGTTGC CAAAGGATGCAGACGCTAATGGTGCCTATTGTATCGCGCTCAAGGGATTGTACGAG ATAAAGCAAATTACGGAGAACTGGAAGGAGGATGGTAAGTTTAGCCGAGACAAGTT GAAGATTAGCAATAAAGACTGGTTTGATTTTATCCAAAACAAGAGGTACCTGAAAC GTCCGGCAGCGACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAG CGGCGCAGGCAGCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGT AAGGTTATTCCGGGCTAA SEQ ID NO: 61 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA TAACGGAACTAATAACTTTCAAAATTTCATAGGTATTTCAAGCTTGCAGAAGACCCT GAGGAATGCCCTGATTCCAACCGAGACAACGCAGCAGTTCATAGTCAAAAATGGCA TTATTAAGGAAGATGAGCTGCGGGGGGAAAACCGACAGATACTCAAGGATATTATG GACGACTATTACCGGGGATTTATCTCAGAAACGCTGAGCAGTATTGATGACATCGAT TGGACCAGTCTTTTCGAGAAAATGGAAATTCAACTTAAGAATGGTGACAATAAAGA CACTCTCATAAAGGAGCAAACTGAATACCGAAAAGCCATACACAAAAAGTTTGCCA ACGATGACCGCTTTAAAAACATGTTTTCAGCTAAGCTCATTAGCGACATTCTCCCCG AGTTTGTGATTCATAACAATAACTATAGCGCATCCGAGAAGGAGGAAAAAACCCAA GTTATCAAATTGTTCAGTAGATTCGCTACGAGCTTTAAAGATTACTTTAAAAACCGG GCTAACTGCTTCAGTGCAGACGATATCAGCTCCTCATCCTGTCATCGCATCGTCAAT GATAATGCTGAGATCTTCTTTTCTAATGCACTGGTTTACCGCAGGATAGTTAAGTCTC TTAGTAACGACGACATCAACAAGATATCAGGAGATATGAAGGATTCCCTTAAAGAA ATGAGTCTCGAGGAGATATATTCTTATGAAAAATACGGCGAATTTATTACCCAAGAG GGCATTAGTTTCTATAATGACATATGCGGAAAAGTTAATAGTTTTATGAATCTCTATT GTCAGAAGAATAAGGAGAATAAGAACCTCTACAAATTGCAGAAGTTGCACAAGCAA ATTCTGTGTATCGCGGACACCTCTTACGAGGTCCCATATAAGTTCGAGAGTGATGAA GAAGTATACCAGAGCGTTAATGGGTTCCTGGACAACATCTCAAGTAAACACATAGT CGAAAGGCTCCGAAAGATCGGTGATAACTATAACGGATATAATTTGGATAAAATTT ATATAGTTAGCAAATTTTACGAGAGCGTCAGTCAGAAGACCTACCGGGACTGGGAG ACCATAAACACAGCGCTGGAAATACATTATAACAACATACTGCCTGGGAACGGTAA GTCAAAGGCAGACAAGGTTAAAAAGGCTGTGAAGAATGACCTGCAAAAATCAATTA CAGAAATAAATGAGTTGGTAAGTAATTACAAACTTTGCAGCGATGATAATATAAAG GCAGAGACGTACATACATGAAATATCTCATATCCTCAACAATTTCGAAGCCCAAGA ACTGAAGTACAACCCGGAAATTCATCTTGTAGAGTCTGAGTTGAAGGCCTCCGAATT GAAAAACGTTCTTGACGTAATTATGAATGCCTTCCACTGGTGCTCAGTATTCATGAC GGAAGAGCTCGTGGATAAAGACAACAATTTTTACGCTGAACTGGAAGAAATATATG ACGAGATTTACCCCGTAATTTCACTCTACAACTTGGTACGAAATTACGTTACCCAAA AGCCATACTCAACAAAAAAAATTAAACTGAACTTCGGGATACCCACCCTCGCAGAT GGATGGTCAAAGTCCAAAGAGTACAGTAACAATGCAATTATCCTGATGCGAGACAA CCTTTATTACCTCGGGATTTTCAACGCTAAAAATAAACCTGATAAAAAAATAATTGA GGGTAATACCTCTGAAAACAAGGGGGATTATAAAAAGATGATATACAATCTGCTGC CTGGCCCGAACAAAATGATTCCTAAAGTCTTCTTGTCTTCCAAGACTGGAGTCGAAA CCTACAAGCCAAGTGCTTATATACTCGAAGGGTACAAACAAAATAAGCACATAAAA TCCAGCAAGGATTTTGATATTACATTCTGCCACGATTTGATTGATTATTTTAAGAACT GTATAGCCATCCACCCAGAATGGAAGAATTTTGGTTTTGATTTTAGCGATACCTCAA CATATGAGGATATCTCTGGCTTTTACCGCGAGGTAGAACTGCAAGGTTATAAGATCG ATTGGACTTATATTTCTGAAAAGGACATAGATCTCCTGCAAGAGAAAGGGCAACTTT ATTTGTTTCAAATATACAACAAAGATTTTAGTAAGAAGAGTACTGGCAATGATAACC TTCACACTATGTATCTGAAGAACCTTTTTTCTGAGGAGAACTTGAAGGACATAGTCC TTAAACTCAATGGGGAAGCTGAAATATTCTTTCGCAAAAGCTCCATTAAAAACCCGA TCATTCATAAAAAGGGTTCCATCTTGGTAAACCGCACATACGAGGCGGAAGAAAAA GATCAGTTCGGAAATATCCAGATCGTAAGGAAGAATATCCCCGAAAATATATACCA AGAGCTTTACAAATATTTTAACGATAAGTCAGACAAGGAACTGTCAGACGAAGCAG CCAAGTTGAAGAATGTCGTAGGGCACCACGAAGCAGCTACAAACATAGTTAAAGAT TATCGGTACACCTACGATAAATATTTCCTGCATATGCCAATAACCATAAACTTCAAA GCCAACAAAACAGGGTTCATCAATGACCGAATACTTCAGTATATAGCCAAGGAAAA AGACCTGCATGTTATAGGAATAGATAGAGGTGAGCGCAACTTGATATATGTCAGCG TGATAGACACCTGCGGAAATATCGTCGAGCAAAAAAGTTTCAACATTGTTAATGGCT ACGATTACCAAATTAAATTGAAGCAGCAAGAGGGGGCTCGGCAAATCGCGCGAAAG GAATGGAAAGAAATCGGGAAGATTAAAGAAATTAAAGAGGGCTACCTGTCTCTTGT AATTCACGAAATATCTAAGATGGTCATCAAGTATAATGCCATTATTGCGATGGAAGA TCTGTCCTACGGATTTAAGAAAGGCAGGTTTAAAGTCGAAAGGCAGGTGTACCAGA AATTCGAGACCATGCTGATTAATAAGCTCAACTATCTCGTATTTAAGGATATTTCTAT AACTGAAAATGGAGGGCTTCTCAAAGGATATCAACTCACATACATACCTGATAAGC TGAAGAACGTAGGCCACCAGTGTGGATGCATATTCTATGTACCAGCTGCATACACAA GCAAGATCGATCCAACTACTGGGTTTGTCAATATCTTCAAATTTAAGGACTTGACGG TCGATGCCAAACGGGAGTTCATCAAAAAGTTTGATAGTATTCGATATGATAGTGAGA AGAACTTGTTTTGCTTCACATTTGACTACAACAATTTCATAACGCAAAATACGGTTA TGTCTAAATCCTCATGGAGCGTCTACACTTACGGAGTGAGGATAAAGCGGCGCTTCG TAAATGGCAGGTTTAGCAATGAATCCGACACGATTGACATAACCAAGGATATGGAG AAAACCCTCGAGATGACCGATATAAATTGGCGGGATGGACACGATCTGCGACAAGA CATAATCGATTATGAAATCGTGCAGCACATATTTGAGATATTCAGGCTTACGGTCCA AATGAGAAATTCCCTTTCCGAACTTGAAGACCGCGATTACGACCGACTGATAAGCCC CGTTCTGAACGAAAATAACATCTTCTACGACAGCGCTAAAGCGGGAGACGCGCTGC CGAAAGATGCGGACGCAAATGGAGCCTATTGTATCGCCTTGAAAGGGTTGTACGAG ATCAAACAGATAACCGAGAATTGGAAGGAGGATGGGAAGTTTAGTCGAGACAAACT TAAAATAAGCAACAAGGACTGGTTCGACTTTATTCAAAACAAACGATATCTCAAAC GTCCGGCAGCGACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAG CGGCGCAGGCAGCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGT AAGGTTATTCCGGGCTAA SEQ ID NO: 62 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA TAATGGTACTAACAATTTTCAAAACTTTATCGGCATCTCTTCACTTCAGAAAACTCTT CGGAACGCCCTTATACCGACGGAGACAACGCAGCAGTTTATAGTTAAAAACGGGAT CATTAAAGAAGATGAACTCAGAGGGGAAAACAGGCAAATATTGAAGGACATTATGG ACGATTACTACCGGGGGTTTATTTCAGAGACCCTTTCATCTATTGATGACATAGATT GGACCTCCCTTTTCGAGAAAATGGAGATACAATTGAAAAACGGCGACAATAAAGAT ACACTTATCAAGGAACAAACTGAGTATCGCAAGGCGATTCACAAGAAGTTTGCGAA TGACGATCGCTTTAAGAATATGTTTTCTGCGAAGCTCATAAGTGACATTCTGCCTGA ATTTGTCATTCATAACAACAATTATTCTGCTAGCGAAAAAGAGGAAAAAACTCAAGT CATTAAGCTTTTTAGCAGGTTCGCTACTAGTTTTAAAGACTATTTTAAGAACCGGGC GAATTGCTTTAGCGCTGACGACATATCATCCTCATCCTGTCATCGCATAGTCAATGA TAATGCAGAAATATTCTTTTCTAATGCGCTCGTGTATCGGAGAATAGTGAAAAGCCT CTCTAACGATGACATTAACAAAATAAGCGGCGATATGAAGGATAGTCTGAAGGAAA TGTCCCTCGAAGAAATATACTCATACGAGAAGTACGGAGAATTTATCACCCAGGAA GGAATTAGTTTTTACAACGACATCTGTGGTAAGGTTAACTCTTTTATGAATCTGTATT GTCAAAAGAATAAAGAAAATAAAAATCTTTATAAGCTCCAAAAGCTTCACAAACAA ATCTTGTGCATTGCGGATACGTCATACGAAGTACCTTACAAATTTGAAAGCGACGAA GAGGTGTATCAGTCAGTGAATGGGTTCCTTGACAATATTTCTAGCAAACATATTGTG GAGCGACTTCGAAAGATCGGTGATAATTACAATGGCTATAATTTGGATAAAATTTAC ATAGTTAGTAAGTTTTATGAATCCGTCTCACAAAAGACGTACCGAGATTGGGAGACC ATCAACACTGCTCTGGAGATTCATTACAATAATATATTGCCTGGGAATGGGAAGTCA AAGGCCGACAAGGTTAAAAAAGCCGTAAAAAACGATCTTCAAAAGTCCATTACCGA GATAAATGAACTTGTATCCAACTATAAGTTGTGCTCTGACGATAATATTAAAGCAGA AACGTATATCCACGAAATAAGTCACATCCTGAACAACTTCGAAGCTCAAGAGCTCA AGTATAATCCTGAAATTCATCTCGTCGAAAGCGAGCTGAAAGCATCCGAGTTGAAG AATGTGCTTGATGTGATCATGAACGCATTCCATTGGTGCAGTGTGTTCATGACCGAA GAACTTGTAGACAAAGACAACAACTTCTACGCTGAATTGGAAGAGATTTACGATGA AATTTACCCCGTGATATCCCTCTATAATCTGGTAAGAAATTACGTCACGCAAAAACC ATACAGTACCAAGAAAATAAAGCTCAACTTTGGTATTCCGACGTTGGCAGATGGGT GGAGTAAGAGCAAGGAGTATTCTAACAATGCAATCATCCTCATGCGCGACAATTTGT ATTATCTGGGGATCTTCAACGCGAAAAATAAGCCCGACAAAAAGATAATAGAAGGC AATACGTCCGAGAACAAAGGGGACTATAAGAAAATGATTTATAACCTTCTTCCAGG ACCCAACAAGATGATCCCAAAGGTTTTCTTGAGTTCAAAAACCGGCGTAGAAACTTA TAAACCGTCCGCCTACATTCTGGAAGGGTACAAGCAAAACAAGCACATTAAGTCAT CTAAGGATTTCGACATTACTTTTTGTCATGATTTGATAGACTACTTCAAAAATTGTAT AGCGATACATCCGGAATGGAAAAATTTTGGGTTCGATTTTTCCGACACAAGTACTTA TGAAGACATCTCAGGGTTTTATAGGGAAGTTGAACTGCAAGGTTACAAAATAGACT GGACTTATATTAGTGAGAAGGACATTGATTTGCTCCAGGAAAAGGGTCAATTGTATC TGTTCCAGATATATAACAAGGATTTCTCTAAAAAATCTACAGGTAACGACAATCTCC ACACGATGTACCTCAAGAATCTCTTCAGCGAAGAGAATTTGAAGGATATCGTACTTA AGCTCAATGGAGAAGCGGAAATATTCTTCAGAAAGTCCAGCATTAAGAATCCTATA ATTCACAAGAAAGGGTCAATTCTCGTAAACCGGACTTATGAGGCCGAAGAAAAAGA TCAGTTTGGTAACATTCAGATTGTACGGAAAAACATTCCCGAGAACATCTATCAAGA ACTGTATAAATACTTTAATGATAAATCCGACAAGGAACTTTCTGACGAGGCTGCAAA ATTGAAGAACGTAGTGGGACACCATGAGGCCGCAACCAATATAGTAAAGGATTACA GATACACTTATGATAAGTATTTCCTCCATATGCCGATCACGATTAATTTCAAGGCGA ATAAAACCGGCTTCATTAACGATCGCATTTTGCAATATATTGCGAAGGAAAAGGATT TGCACGTGATAGGTATAGACCGGGGTGAACGAAACTTGATTTACGTCTCTGTGATCG ACACATGCGGAAATATAGTTGAACAGAAGTCCTTTAATATTGTGAATGGTTACGACT ACCAGATAAAATTGAAGCAACAGGAGGGCGCAAGACAGATAGCTCGCAAAGAGTG GAAGGAAATCGGCAAGATCAAAGAAATAAAGGAGGGTTATCTTTCCCTGGTAATTC ATGAAATTAGCAAGATGGTTATTAAGTATAATGCTATAATAGCTATGGAGGACCTTT CCTATGGGTTCAAGAAAGGTCGCTTCAAAGTGGAGCGACAAGTGTATCAAAAGTTC GAGACTATGTTGATAAATAAATTGAATTATTTGGTTTTTAAAGACATTTCAATAACT GAGAACGGGGGTCTCTTGAAGGGGTACCAATTGACTTATATTCCGGACAAGTTGAA GAATGTCGGACACCAGTGTGGTTGCATTTTCTACGTGCCTGCCGCTTACACCTCAAA AATCGATCCGACCACTGGTTTTGTAAATATATTTAAATTCAAAGATCTCACCGTTGA TGCCAAACGGGAGTTTATCAAAAAATTCGATTCCATTCGCTACGACTCTGAGAAAAA CCTTTTTTGTTTCACGTTCGATTATAACAACTTTATAACCCAAAATACTGTAATGTCC AAGTCAAGTTGGTCTGTCTATACTTACGGAGTAAGGATCAAGCGCCGCTTCGTTAAT GGGAGATTCTCAAACGAGTCTGATACCATAGACATAACTAAAGACATGGAAAAAAC CCTGGAAATGACGGACATCAATTGGCGAGACGGGCATGATCTTCGACAGGACATAA TAGATTACGAAATTGTTCAACACATTTTCGAGATATTTCGACTTACGGTTCAGATGA GGAATTCCCTTTCCGAATTGGAAGACCGGGATTATGATCGACTTATATCTCCCGTGC TCAATGAAAACAATATTTTTTATGATTCAGCGAAAGCTGGGGACGCGCTGCCAAAA GATGCCGATGCCAATGGAGCATACTGTATCGCCCTGAAGGGTTTGTATGAGATTAAG CAAATTACTGAAAACTGGAAGGAAGATGGCAAGTTTTCTAGAGATAAGCTTAAGAT TAGCAATAAGGACTGGTTTGACTTCATTCAAAATAAAAGGTATCTTAAACGTCCGGC AGCGACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCA GGCAGCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTA TTCCGGGCTAA SEQ ID NO: 63 ATGGGCCATCATCATCATCATCACAGCAGCGGCGTCGATCTGGGTACCGAGAATTTG TATTTCCAGAGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAA TAATGGAACAAATAATTTTCAAAATTTTATTGGTATCAGTTCATTGCAAAAGACTTT GAGAAATGCTTTGATCCCGACTGAGACCACACAGCAGTTCATCGTCAAAAATGGCA TAATCAAGGAAGACGAACTTAGGGGTGAGAATAGACAAATATTGAAGGACATCATG GATGACTATTATAGGGGGTTCATTTCCGAAACGCTCAGTAGTATTGATGACATTGAC TGGACTAGTCTTTTCGAGAAAATGGAAATTCAGCTTAAGAACGGGGACAATAAAGA CACGCTGATCAAGGAGCAAACGGAATATAGGAAGGCGATCCATAAAAAATTCGCGA ATGATGATCGGTTTAAAAACATGTTTAGTGCCAAGTTGATCAGCGACATACTGCCCG AATTCGTGATCCACAACAATAATTACAGCGCCTCCGAAAAGGAGGAAAAAACTCAG GTCATTAAATTGTTTAGCCGATTCGCAACGAGTTTCAAAGATTATTTTAAGAACCGG GCCAACTGTTTTTCAGCGGATGATATTAGCTCCAGCAGCTGCCATCGCATAGTAAAT GATAACGCTGAAATCTTTTTTAGCAACGCACTTGTCTACCGGAGGATTGTAAAATCA CTGTCAAATGATGACATTAACAAAATATCTGGAGATATGAAGGACTCACTCAAAGA AATGAGCCTGGAAGAAATATATTCATACGAAAAATACGGGGAGTTTATTACCCAGG AAGGTATCAGTTTTTATAATGATATATGTGGAAAAGTTAATTCATTTATGAATCTTTA CTGTCAAAAAAATAAGGAGAACAAGAATTTGTACAAGCTCCAAAAACTTCATAAAC AGATTCTGTGCATCGCAGACACAAGTTATGAGGTACCGTACAAATTTGAGAGCGAC GAAGAAGTTTATCAGAGTGTGAATGGTTTCCTGGACAATATCTCTTCTAAACACATT GTTGAGAGGCTTAGGAAGATCGGTGATAATTATAACGGCTATAATCTGGACAAAAT TTATATTGTATCAAAGTTTTATGAATCAGTCTCTCAAAAGACGTATCGGGATTGGGA AACAATTAACACGGCTCTGGAGATCCACTACAATAACATTCTGCCCGGCAACGGGA AGAGCAAAGCTGATAAGGTCAAGAAGGCAGTCAAGAACGACCTTCAGAAGAGCAT AACAGAAATTAACGAATTGGTCAGTAACTACAAACTGTGTAGTGATGACAACATAA AAGCCGAAACATACATCCATGAAATAAGCCATATCCTGAATAACTTCGAAGCCCAA GAACTTAAATACAATCCCGAGATTCATCTTGTCGAATCAGAACTCAAGGCGTCCGAG CTCAAAAATGTCCTTGACGTGATAATGAATGCCTTCCACTGGTGCAGCGTATTCATG ACGGAGGAGTTGGTAGATAAAGACAACAACTTTTATGCCGAATTGGAAGAGATTTA TGATGAGATTTACCCCGTTATTTCTCTGTACAACTTGGTTCGAAACTACGTAACACA AAAACCATACTCAACCAAAAAGATCAAACTCAATTTTGGCATACCTACATTGGCTGA TGGTTGGTCCAAGTCAAAGGAATATAGCAATAATGCAATAATTCTCATGCGAGATA ACTTGTATTATTTGGGGATCTTTAACGCTAAGAACAAACCAGATAAAAAGATAATCG AGGGGAACACAAGTGAGAACAAGGGTGATTACAAAAAAATGATTTACAATCTGCTT CCTGGGCCTAACAAAATGATTCCGAAGGTGTTTCTTAGCTCTAAAACTGGAGTGGAG ACGTATAAGCCTTCCGCGTACATTCTCGAAGGCTACAAGCAAAATAAGCATATCAA GTCCAGTAAGGACTTCGACATCACTTTTTGCCACGATCTCATCGATTACTTTAAGAA CTGTATCGCAATACACCCCGAGTGGAAAAACTTTGGTTTTGATTTTTCAGACACTAG TACCTACGAGGACATTTCCGGCTTCTATCGAGAAGTCGAACTCCAGGGCTACAAAAT CGATTGGACGTACATTTCTGAGAAGGACATCGACTTGCTCCAAGAGAAAGGTCAAC TTTACCTCTTCCAAATTTACAATAAAGACTTTTCAAAGAAGAGCACCGGTAATGACA ACTTGCATACCATGTATCTGAAGAACCTGTTTTCTGAGGAGAACCTCAAGGATATTG TATTGAAGTTGAATGGCGAAGCAGAAATATTTTTCCGAAAGTCATCTATCAAGAACC CCATTATACACAAAAAAGGCTCTATCCTGGTGAACCGGACTTACGAGGCAGAGGAG AAGGATCAATTCGGAAACATACAGATAGTCCGCAAAAACATCCCTGAGAATATCTA TCAGGAACTCTATAAGTACTTCAATGATAAATCAGACAAGGAGCTTAGCGACGAAG CAGCTAAACTTAAAAACGTGGTTGGCCATCACGAGGCCGCTACCAACATAGTCAAA GACTACCGCTATACTTATGACAAGTACTTTTTGCACATGCCCATAACAATTAATTTCA AAGCTAACAAAACAGGGTTTATAAATGACAGAATCCTCCAATACATCGCCAAAGAG AAGGACCTCCATGTAATCGGGATTGATAGAGGCGAACGGAACTTGATTTACGTTAGT GTCATTGATACCTGTGGTAACATTGTCGAACAAAAGTCATTCAACATAGTCAATGGA TATGATTATCAGATAAAACTCAAGCAACAAGAAGGCGCGAGGCAGATTGCCAGGAA GGAATGGAAAGAAATCGGGAAGATCAAGGAGATCAAGGAGGGTTACCTGTCCTTGG TGATACACGAGATTTCAAAAATGGTTATAAAATACAATGCCATTATCGCGATGGAG GATTTGTCTTATGGATTTAAGAAGGGGAGGTTCAAAGTCGAACGACAAGTCTATCAG AAGTTTGAAACAATGCTCATTAACAAGCTCAATTACCTTGTTTTCAAGGATATAAGC ATCACTGAAAACGGCGGACTCCTTAAGGGATATCAGCTGACTTATATCCCCGACAAG CTCAAGAACGTAGGGCACCAATGCGGATGCATCTTTTACGTGCCTGCAGCATATACT TCAAAAATTGATCCGACTACTGGCTTTGTTAACATTTTCAAGTTCAAGGATCTGACG GTAGACGCTAAGAGAGAATTCATAAAAAAGTTTGACAGCATCAGGTACGATAGTGA AAAGAACCTTTTTTGTTTTACCTTTGACTACAATAATTTTATTACGCAAAATACAGTT ATGAGCAAATCAAGTTGGAGCGTTTACACATATGGCGTTCGGATCAAGCGCAGATTC GTCAATGGTCGCTTCTCAAATGAGAGCGATACAATCGATATAACGAAGGATATGGA GAAGACGCTTGAGATGACAGATATCAACTGGCGGGACGGACATGACCTTAGACAAG ACATAATCGATTACGAAATAGTACAGCATATCTTTGAGATTTTTAGGCTTACAGTTC AGATGCGGAACTCTCTTTCCGAACTGGAGGACCGGGATTATGATCGGTTGATCTCCC CAGTACTGAACGAAAATAATATCTTTTACGATAGCGCGAAGGCTGGTGATGCACTCC CAAAAGACGCTGATGCGAACGGAGCTTATTGCATAGCCCTTAAAGGGCTTTACGAG ATTAAACAAATAACAGAAAATTGGAAGGAAGATGGCAAATTTTCCCGCGACAAGTT GAAGATTAGTAACAAAGACTGGTTCGACTTCATTCAGAATAAACGCTACCTCAAAC GTCCGGCAGCGACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAG CGGCGCAGGCAGCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGT AAGGTTATTCCGGGCTAA SEQ ID NO: 64 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAATAACGGTA CCAATAACTTCCAGAACTTCATCGGTATTTCTAGCCTGCAAAAGACCCTGCGTAACG CGCTGATTCCGACCGAGACTACCCAGCAATTCATCGTGAAAAACGGTATCATTAAGG AAGATGAATTGCGCGGTGAGAATCGTCAGATTCTGAAAGATATCATGGATGACTAC TATCGCGGTTTCATTAGCGAAACCCTGTCGAGCATCGATGATATCGATTGGACGAGC CTCTTCGAGAAAATGGAAATTCAACTGAAAAATGGTGACAACAAAGATACCCTGAT TAAAGAACAAACGGAATACCGCAAGGCAATCCATAAAAAGTTTGCGAATGACGACC GTTTTAAGAATATGTTCTCGGCCAAGCTGATTTCCGACATCCTGCCAGAGTTCGTCAT TCACAACAACAATTACAGCGCAAGCGAGAAAGAGGAAAAGACTCAGGTCATTAAGC TGTTTAGCCGCTTTGCGACGTCCTTCAAAGACTACTTCAAGAATCGTGCGAATTGCTT TAGCGCGGATGACATCTCTAGCTCTAGCTGTCACCGTATTGTTAACGACAATGCAGA GATTTTCTTCAGCAACGCCCTGGTGTATCGCCGTATTGTCAAGTCTCTGAGCAACGA CGACATTAACAAGATCAGCGGCGACATGAAAGACAGCCTGAAAGAAATGTCTCTGG AAGAAATCTACAGCTACGAGAAATATGGTGAGTTTATCACCCAAGAGGGCATTAGC TTCTACAATGATATCTGTGGTAAGGTTAATAGCTTTATGAATCTGTACTGCCAGAAG AATAAAGAAAACAAGAACTTGTACAAGCTGCAAAAGCTGCATAAGCAAATTCTGTG CATCGCCGATACTAGCTATGAAGTTCCGTACAAGTTCGAGTCTGATGAAGAGGTGTA TCAGTCAGTCAACGGTTTTCTGGATAACATCAGCAGCAAGCACATCGTCGAGCGCCT GCGCAAGATTGGTGACAACTACAATGGTTATAACCTGGACAAGATCTATATCGTGTC GAAGTTTTACGAGAGCGTGTCCCAGAAAACGTACCGTGATTGGGAAACGATTAACA CGGCCTTGGAAATTCACTATAACAATATCCTGCCGGGCAACGGCAAGAGCAAAGCT GACAAAGTCAAAAAAGCTGTGAAAAACGATCTGCAAAAGTCCATCACCGAGATCAA CGAACTGGTTAGCAACTATAAGCTGTGTAGCGACGACAACATTAAAGCTGAAACGT ATATCCACGAAATCAGCCACATCCTGAATAACTTTGAGGCACAAGAACTGAAATAC AATCCTGAGATCCATCTGGTAGAGAGCGAGCTGAAGGCAAGCGAGTTGAAAAACGT TCTCGACGTTATCATGAATGCTTTCCACTGGTGTAGCGTGTTTATGACCGAAGAACT GGTTGACAAAGATAACAATTTCTATGCAGAGCTGGAAGAAATCTATGATGAAATCT ACCCGGTCATCAGCCTGTATAACCTGGTTCGTAACTACGTGACGCAGAAGCCGTACA GCACCAAAAAGATCAAGCTGAACTTCGGTATTCCGACCTTGGCGGACGGTTGGAGC AAATCCAAAGAATACTCCAATAATGCGATTATTCTGATGCGTGATAATCTGTACTAT CTGGGTATCTTCAATGCGAAGAACAAGCCAGATAAAAAGATTATTGAAGGCAACAC CAGCGAGAATAAAGGCGACTACAAGAAAATGATCTACAACTTATTGCCGGGTCCGA ACAAGATGATCCCGAAAGTTTTTCTGAGCAGCAAGACCGGCGTTGAAACCTATAAG CCGAGCGCGTACATTTTAGAGGGCTATAAACAAAACAAGCACATCAAGAGCAGCAA AGATTTTGATATTACGTTCTGCCACGACCTGATCGACTATTTCAAGAATTGTATTGCG ATTCACCCTGAGTGGAAGAACTTCGGTTTTGACTTTTCCGATACCTCCACCTATGAA GATATTAGCGGTTTTTACCGTGAAGTCGAGTTGCAGGGTTATAAGATTGATTGGACT TACATTTCCGAGAAAGACATCGACCTGTTGCAAGAGAAAGGTCAGCTGTACCTGTTT CAGATCTATAACAAAGATTTCAGCAAAAAGTCGACGGGCAATGATAATCTGCACAC CATGTATCTGAAAAACCTGTTTAGCGAAGAGAACCTGAAAGACATTGTTCTTAAGCT GAATGGTGAGGCCGAGATCTTCTTCCGTAAAAGCTCCATTAAGAACCCGATTATCCA CAAAAAGGGCTCTATTCTGGTTAACCGCACGTACGAAGCGGAAGAGAAAGATCAAT TTGGTAACATCCAGATCGTGCGTAAGAATATCCCGGAGAACATTTACCAAGAACTGT ATAAGTATTTCAATGACAAGAGCGATAAAGAATTGAGCGATGAAGCGGCAAAGCTG AAAAACGTCGTTGGCCACCACGAAGCCGCGACGAATATCGTGAAAGATTATCGTTA CACCTACGACAAGTACTTTCTGCACATGCCGATCACCATCAATTTCAAAGCGAATAA AACGGGTTTTATCAATGACCGTATCCTGCAGTACATTGCGAAAGAAAAAGATTTACA CGTGATTGGTATTGATCGCGGCGAGCGCAATCTGATTTACGTCAGCGTTATCGACAC GTGCGGCAATATTGTGGAGCAGAAAAGCTTCAATATCGTCAATGGTTACGACTACCA GATCAAACTGAAGCAACAAGAGGGCGCCCGCCAGATTGCGCGTAAAGAGTGGAAA GAAATCGGTAAGATTAAAGAAATCAAGGAAGGCTACCTGTCCCTGGTGATCCATGA AATCAGCAAAATGGTGATCAAGTACAACGCTATCATTGCGATGGAAGATCTGAGCT ACGGTTTTAAAAAGGGTCGCTTCAAAGTTGAGCGTCAAGTGTATCAGAAATTTGAGA CTATGCTGATTAACAAGTTGAACTATCTGGTTTTTAAAGACATCAGCATTACCGAGA ATGGTGGCCTGCTGAAGGGTTATCAACTGACCTATATTCCTGACAAGTTGAAAAATG TTGGTCATCAGTGTGGTTGCATTTTCTACGTACCGGCAGCGTACACGAGCAAGATTG ACCCGACCACGGGTTTCGTTAACATTTTCAAGTTTAAAGATTTGACCGTGGACGCCA AGCGTGAGTTCATTAAAAAGTTCGACAGCATCAGATACGACTCTGAGAAGAATCTG TTCTGCTTTACGTTCGACTACAATAACTTCATTACCCAAAATACCGTTATGAGCAAA AGCTCCTGGAGCGTGTACACGTACGGCGTCCGTATCAAGCGTCGTTTTGTGAATGGT CGCTTTTCCAACGAATCTGACACCATTGACATTACCAAAGATATGGAAAAGACCCTT GAGATGACCGACATTAATTGGCGTGATGGCCATGACTTGCGCCAAGACATTATCGAC TACGAAATTGTTCAGCACATCTTTGAGATTTTTCGTCTGACGGTCCAGATGCGCAAC TCGCTGAGCGAGTTGGAAGATCGTGACTATGACCGTCTGATTAGCCCGGTGCTGAAT GAAAACAATATCTTCTATGATAGCGCAAAGGCCGGTGACGCGCTGCCGAAAGATGC GGATGCTAACGGTGCATACTGCATTGCACTGAAGGGTCTGTACGAAATCAAACAGA TCACCGAGAATTGGAAAGAGGATGGTAAGTTTAGCCGTGATAAGCTGAAGATTAGC AATAAAGACTGGTTCGACTTTATTCAAAACAAGCGCTATCTGAAACGTCCGGCAGCG ACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCA GCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCG GGCTAA SEQ ID NO: 65 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAACGGAA CAAATAATTTTCAGAACTTTATTGGGATCAGTTCGCTTCAGAAAACGCTTCGTAATG CTCTGATTCCCACAGAAACCACTCAGCAGTTTATCGTAAAGAATGGCATTATCAAGG AGGATGAATTACGCGGCGAGAACCGCCAAATCTTAAAAGATATCATGGACGACTAC TACCGCGGTTTCATTAGCGAAACTCTTAGTTCAATTGACGACATTGACTGGACGTCC TTGTTCGAAAAGATGGAGATTCAATTAAAGAACGGTGATAACAAGGATACGTTGAT TAAAGAACAGACGGAGTACCGTAAGGCTATCCACAAAAAATTTGCAAACGACGACC GCTTTAAAAATATGTTTAGCGCAAAATTAATCTCCGACATCCTGCCTGAATTCGTCA TCCATAACAATAACTATAGCGCCTCGGAAAAAGAAGAAAAAACGCAGGTTATTAAA CTTTTCTCGCGCTTTGCAACAAGCTTTAAGGATTACTTCAAAAATCGCGCCAATTGTT TTTCAGCCGACGACATTAGCTCCAGTTCCTGCCACCGTATTGTGAATGACAACGCTG AGATTTTTTTTTCCAATGCGCTGGTTTATCGTCGTATTGTTAAGAGCCTTAGTAACGA CGACATTAATAAAATTAGCGGTGATATGAAGGATAGCTTGAAAGAAATGAGTCTGG AAGAGATCTATAGTTACGAGAAGTACGGCGAATTTATTACCCAGGAGGGCATTTCAT TTTACAATGATATCTGTGGAAAAGTCAACTCCTTTATGAACTTGTATTGCCAAAAGA ATAAAGAAAACAAAAACCTGTACAAACTGCAAAAGTTACACAAGCAGATTTTGTGT ATCGCAGACACGTCATACGAAGTACCGTACAAGTTTGAGTCCGATGAAGAAGTGTA CCAAAGCGTTAATGGCTTTTTGGATAACATTTCGAGCAAACATATCGTAGAGCGTTT GCGTAAGATTGGTGATAATTACAACGGTTACAATTTAGACAAAATCTATATCGTCTC TAAGTTTTACGAAAGTGTTTCTCAGAAAACTTACCGCGATTGGGAGACGATCAACAC TGCGCTGGAGATTCATTACAATAATATCCTTCCAGGTAACGGTAAAAGCAAAGCTGA TAAGGTGAAAAAGGCGGTTAAAAATGACCTTCAAAAGTCTATCACAGAAATCAACG AATTGGTCAGCAATTATAAGCTTTGCAGTGACGATAACATTAAGGCCGAGACTTACA TCCATGAGATCTCTCACATTCTTAATAATTTTGAAGCGCAAGAGCTGAAATACAATC CTGAAATCCATCTGGTCGAAAGTGAATTAAAAGCCTCCGAATTAAAAAATGTCTTGG ACGTGATCATGAATGCGTTCCATTGGTGCTCAGTTTTTATGACGGAAGAGTTGGTGG ACAAAGACAACAATTTTTACGCCGAGCTTGAGGAAATTTACGACGAAATTTACCCCG TTATTTCGTTATACAACCTTGTGCGTAATTACGTTACACAAAAGCCCTATTCGACAA AGAAAATCAAGTTAAATTTCGGGATTCCCACATTAGCTGATGGATGGTCCAAATCCA AAGAATACTCGAATAACGCTATCATCCTTATGCGTGATAATTTGTACTACTTAGGCA TCTTCAATGCGAAGAACAAACCTGACAAGAAAATTATCGAAGGAAACACTTCGGAG AACAAAGGTGATTATAAAAAGATGATCTACAACTTGCTTCCCGGGCCAAACAAAAT GATTCCCAAGGTATTTTTGAGTTCTAAAACCGGTGTCGAAACTTACAAACCAAGTGC TTATATTTTGGAAGGATACAAACAGAACAAACATATCAAGTCTTCGAAAGACTTCGA TATTACGTTCTGCCACGATCTGATCGATTACTTCAAGAACTGTATTGCTATTCACCCC GAGTGGAAGAACTTTGGATTTGATTTCTCCGACACGTCCACTTATGAAGATATCTCT GGCTTCTATCGCGAGGTTGAATTACAAGGGTATAAGATTGACTGGACTTATATTTCG GAGAAGGATATCGATCTTTTGCAAGAAAAAGGGCAACTTTATTTATTTCAGATCTAT AACAAGGACTTTTCAAAAAAGAGCACTGGAAATGACAATCTGCATACCATGTACCT TAAGAACCTGTTCTCGGAAGAGAACCTGAAGGACATTGTACTTAAACTGAATGGAG AGGCAGAGATCTTCTTTCGCAAATCAAGCATTAAGAACCCAATTATTCACAAAAAG GGGAGTATCTTAGTAAATCGCACATATGAGGCTGAGGAAAAAGATCAGTTTGGTAA CATTCAGATCGTGCGTAAGAACATTCCTGAAAATATCTATCAGGAACTTTATAAGTA TTTCAACGATAAAAGTGATAAAGAGCTGAGTGACGAAGCGGCTAAACTTAAGAATG TTGTGGGACACCATGAGGCAGCAACCAATATTGTGAAGGATTATCGCTATACGTACG ACAAATACTTTTTACACATGCCCATCACTATTAATTTTAAAGCTAATAAGACTGGCTT CATTAACGATCGCATCCTGCAGTACATTGCTAAGGAAAAGGATCTTCACGTTATCGG TATCGATCGCGGGGAGCGTAATCTTATCTACGTCTCTGTCATTGACACGTGTGGCAA TATTGTGGAGCAAAAGTCCTTCAATATTGTTAACGGCTATGACTATCAGATTAAATT GAAACAGCAGGAAGGTGCGCGTCAGATTGCCCGCAAGGAATGGAAGGAAATTGGC AAGATCAAAGAAATTAAGGAGGGCTACTTAAGCTTAGTAATTCACGAAATTAGTAA AATGGTTATCAAATACAACGCCATCATCGCGATGGAGGATCTTTCGTACGGGTTTAA GAAAGGTCGTTTTAAAGTGGAGCGTCAGGTGTACCAGAAATTTGAAACTATGCTTAT TAACAAACTTAACTACCTGGTTTTCAAGGATATCAGTATTACTGAAAACGGGGGGCT GTTAAAAGGGTATCAATTAACTTACATTCCAGACAAATTAAAGAACGTTGGACATCA GTGTGGCTGCATTTTTTATGTACCAGCTGCATACACTTCAAAGATCGATCCTACGACT GGGTTCGTGAACATTTTTAAGTTTAAAGACTTGACGGTAGATGCCAAGCGCGAATTC ATCAAGAAATTCGACAGCATTCGCTACGACTCTGAGAAAAATCTTTTCTGTTTCACA TTCGATTATAACAATTTCATTACGCAGAACACAGTAATGTCCAAGTCTTCTTGGAGT GTTTATACATATGGTGTCCGCATTAAGCGCCGTTTCGTCAACGGCCGCTTCAGTAAT GAGAGCGATACTATTGACATCACAAAAGACATGGAAAAAACACTGGAAATGACCGA CATCAATTGGCGTGACGGCCATGACTTACGTCAGGATATCATTGATTATGAGATCGT TCAACACATCTTCGAAATCTTTCGCTTGACTGTTCAAATGCGCAATTCCTTGTCGGAA TTGGAGGACCGTGATTATGACCGCTTAATTTCCCCCGTCTTAAATGAAAACAATATT TTTTATGACTCTGCAAAAGCTGGAGATGCTCTGCCGAAAGACGCCGATGCAAATGG GGCATATTGCATTGCTTTAAAGGGGCTTTACGAGATCAAGCAAATCACCGAAAACTG GAAAGAGGATGGAAAGTTTTCGCGTGATAAACTGAAGATCTCTAACAAAGACTGGT TCGACTTTATCCAGAACAAGCGTTATTTGAAACGTCCGGCAGCGACCAAAAAAGCC GGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAAGA AACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 66 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAACGGCA CCAATAACTTCCAAAACTTCATCGGGATCTCTAGCCTTCAGAAGACGCTTCGCAATG CTCTTATCCCAACTGAGACCACTCAACAATTTATTGTGAAGAATGGAATTATTAAAG AGGACGAACTGCGTGGCGAGAATCGTCAGATCTTAAAGGACATTATGGATGATTAT TACCGTGGATTCATCTCCGAAACATTATCGTCGATCGATGATATCGATTGGACTTCTC TGTTCGAGAAAATGGAAATTCAATTGAAAAACGGAGATAATAAAGATACGCTTATC AAAGAACAGACGGAATATCGTAAAGCGATTCATAAGAAATTCGCAAATGACGATCG TTTCAAAAATATGTTCAGTGCCAAGCTTATTTCGGACATTTTACCTGAATTTGTAATT CATAATAATAACTACTCAGCAAGTGAGAAGGAGGAGAAAACCCAAGTTATTAAACT GTTCTCTCGTTTCGCAACGTCCTTTAAAGATTACTTTAAAAACCGCGCGAATTGCTTT AGCGCTGACGACATTTCCAGCTCATCCTGTCATCGCATCGTAAACGACAATGCGGAA ATCTTCTTCAGCAACGCCCTGGTTTACCGCCGCATCGTCAAAAGCTTATCGAATGAC GACATCAATAAGATCTCAGGAGATATGAAGGACTCGCTTAAGGAGATGTCTCTGGA GGAAATTTATAGTTACGAAAAGTATGGAGAGTTCATTACCCAGGAGGGAATCTCGTT CTACAATGACATTTGCGGGAAGGTGAACTCCTTCATGAACTTATACTGCCAGAAAAA CAAAGAGAACAAAAATCTGTATAAATTGCAGAAATTACATAAACAGATTCTTTGTAT TGCTGACACTTCCTACGAAGTACCCTATAAATTCGAGTCAGATGAAGAAGTATACCA GTCCGTGAACGGATTTCTGGACAATATCTCCTCAAAACACATCGTGGAACGCTTACG TAAAATTGGCGATAATTATAATGGTTACAATCTTGACAAAATTTATATCGTATCTAA ATTTTACGAGAGTGTGAGCCAAAAGACCTACCGCGACTGGGAGACCATCAACACAG CTTTAGAAATTCACTATAATAATATCTTACCCGGCAATGGTAAGAGCAAGGCTGACA AGGTAAAAAAGGCCGTCAAGAATGATTTGCAGAAATCTATTACAGAAATTAATGAG TTAGTCTCCAACTATAAGCTTTGTTCCGACGATAACATCAAAGCTGAGACATATATT CATGAGATTAGTCACATTCTTAACAACTTCGAGGCCCAGGAACTTAAGTACAATCCT GAAATTCATCTTGTCGAGTCTGAGCTGAAAGCTAGTGAATTGAAAAATGTTTTAGAC GTTATTATGAACGCATTCCACTGGTGCTCTGTGTTTATGACAGAAGAACTGGTCGAC AAGGACAATAACTTCTATGCCGAACTTGAGGAAATCTACGATGAAATTTACCCTGTA ATCTCCTTGTATAATCTTGTACGTAATTACGTCACTCAAAAACCTTACAGCACGAAA AAAATTAAATTGAACTTCGGGATTCCTACACTTGCCGACGGGTGGTCTAAATCCAAG GAATATAGCAACAATGCCATTATTTTAATGCGCGACAATCTTTACTATTTAGGAATT TTTAACGCTAAGAACAAGCCCGATAAAAAGATTATTGAAGGAAACACGTCTGAAAA TAAGGGCGACTACAAAAAGATGATTTATAACCTTTTGCCCGGTCCAAACAAAATGAT CCCAAAGGTATTCCTGTCATCCAAAACAGGGGTTGAGACATATAAGCCCAGCGCAT ATATTCTGGAAGGATACAAACAGAATAAACATATCAAAAGCAGCAAAGATTTTGAC ATTACTTTTTGCCACGATTTAATCGACTACTTCAAAAACTGTATCGCTATCCACCCTG AATGGAAGAATTTCGGATTTGATTTCTCAGATACAAGTACGTATGAGGATATCAGCG GTTTCTATCGCGAAGTTGAACTTCAAGGGTATAAAATTGACTGGACCTACATTAGTG AGAAGGACATCGACCTGTTACAGGAAAAAGGCCAATTGTACTTGTTTCAGATCTACA ATAAGGATTTCTCAAAAAAATCGACCGGCAATGATAACTTGCACACCATGTACCTGA AGAACCTTTTTTCGGAGGAAAACCTTAAAGACATTGTCCTGAAGTTGAATGGAGAA GCGGAGATTTTCTTTCGTAAGTCTTCCATTAAAAATCCAATTATTCATAAGAAGGGC AGCATCCTTGTGAACCGTACGTACGAGGCGGAAGAGAAGGACCAATTCGGTAACAT TCAAATCGTCCGCAAGAACATCCCTGAAAATATTTATCAGGAGCTTTACAAGTATTT CAATGATAAGTCCGACAAGGAATTATCAGATGAGGCTGCGAAGTTGAAAAATGTTG TTGGTCATCACGAGGCGGCGACGAATATTGTAAAGGATTATCGCTACACTTATGACA AGTACTTTCTGCACATGCCGATCACCATTAATTTCAAGGCGAACAAAACAGGATTTA TTAATGACCGCATCTTACAATACATTGCCAAAGAAAAGGACTTACACGTTATTGGCA TTGATCGTGGAGAACGCAACTTAATCTACGTAAGCGTTATTGACACTTGCGGGAATA TCGTAGAACAAAAGAGCTTCAACATCGTGAATGGTTACGATTACCAGATCAAGCTTA AGCAGCAGGAGGGAGCGCGCCAGATCGCGCGCAAGGAATGGAAGGAGATTGGTAA GATCAAGGAAATCAAGGAAGGTTATCTGTCCTTGGTAATCCACGAAATTTCGAAAAT GGTTATCAAATACAATGCTATTATTGCAATGGAGGACTTGTCCTACGGCTTTAAAAA AGGACGCTTTAAGGTGGAGCGCCAGGTTTATCAAAAGTTTGAAACAATGCTGATTA ACAAGCTGAACTATTTGGTCTTTAAAGATATCTCCATCACCGAAAATGGTGGGCTTT TGAAAGGCTATCAACTTACATATATCCCTGATAAGCTTAAGAATGTGGGTCATCAGT GCGGGTGCATTTTTTATGTTCCTGCAGCCTACACGTCCAAAATCGATCCTACAACTG GATTTGTTAATATCTTCAAATTTAAGGATCTTACCGTCGACGCGAAGCGCGAATTTA TCAAGAAATTCGATAGTATTCGTTATGATTCCGAAAAAAACCTTTTCTGTTTCACCTT TGATTATAATAACTTTATCACGCAAAATACTGTCATGAGCAAATCGAGTTGGTCTGT GTACACTTACGGAGTACGCATCAAGCGTCGTTTTGTTAATGGGCGCTTCAGTAACGA GTCAGACACGATTGATATCACAAAAGATATGGAGAAAACGCTGGAGATGACAGACA TCAATTGGCGCGATGGTCATGACTTACGTCAAGACATTATCGATTATGAAATTGTCC AGCATATCTTTGAGATCTTTCGTTTGACTGTTCAGATGCGCAACAGCCTGTCAGAATT GGAGGATCGTGACTATGATCGCCTTATTTCTCCCGTCTTAAATGAGAACAATATCTT CTACGACTCAGCCAAGGCTGGAGATGCACTGCCAAAAGACGCCGACGCAAATGGGG CCTACTGTATTGCATTGAAGGGGTTGTACGAGATCAAACAGATTACAGAAAATTGG AAGGAGGACGGTAAGTTCTCTCGTGATAAGCTGAAGATTTCTAACAAAGACTGGTTC GATTTCATTCAGAACAAACGTTACCTGAAACGTCCGGCAGCGACCAAAAAAGCCGG CCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAAGAAA CGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 67 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAACGGTA CCAATAACTTTCAGAATTTCATTGGAATCAGCAGCTTACAGAAAACCCTGCGCAATG CACTTATCCCCACTGAGACAACCCAGCAGTTCATTGTAAAGAACGGGATTATTAAAG AAGATGAGCTTCGCGGGGAGAATCGTCAGATCTTAAAGGATATTATGGACGATTAC TACCGTGGCTTCATTTCGGAGACGCTGTCGTCGATCGACGACATCGACTGGACATCC TTGTTTGAAAAGATGGAAATCCAACTGAAGAATGGCGATAACAAGGACACGTTAAT CAAAGAGCAGACGGAATACCGTAAAGCTATCCACAAAAAGTTCGCTAATGACGACC GCTTTAAGAACATGTTCTCAGCAAAACTTATTAGCGATATTTTACCTGAATTTGTCAT CCACAATAACAATTACTCCGCGAGTGAAAAAGAGGAGAAAACCCAGGTGATTAAGC TGTTTTCCCGTTTTGCAACCAGTTTCAAGGACTATTTTAAGAATCGTGCTAATTGTTT CTCTGCAGACGACATTTCCTCGTCGTCCTGCCATCGCATTGTTAATGATAATGCTGAA ATCTTTTTTTCAAACGCACTTGTGTATCGTCGCATTGTCAAAAGCTTAAGTAATGACG ATATCAATAAGATCTCAGGAGACATGAAGGACTCCCTGAAAGAAATGTCATTGGAA GAAATTTACTCTTATGAAAAGTATGGAGAATTTATTACGCAGGAGGGTATCAGCTTC TATAACGACATTTGTGGTAAAGTGAACAGCTTTATGAATCTTTATTGTCAAAAGAAT AAAGAGAACAAAAATCTGTACAAGCTGCAGAAATTGCATAAACAAATTCTGTGCAT TGCAGATACTTCGTATGAGGTTCCTTACAAATTCGAGTCGGATGAGGAGGTGTATCA AAGCGTAAACGGATTTTTGGATAACATTAGTAGTAAGCATATTGTGGAACGCCTTCG CAAGATTGGTGACAACTATAACGGATACAACTTAGACAAGATCTATATTGTCTCGAA GTTTTACGAAAGTGTTTCCCAAAAGACTTATCGCGACTGGGAGACAATCAACACTGC GCTGGAAATTCACTATAACAATATCTTGCCGGGGAACGGAAAAAGTAAGGCAGATA AGGTGAAGAAAGCAGTCAAAAATGATCTGCAAAAAAGCATTACTGAAATTAACGAA CTTGTGTCAAATTACAAATTGTGTTCGGATGACAATATTAAAGCGGAAACGTATATC CACGAGATCTCGCACATTCTTAATAATTTCGAGGCGCAGGAATTAAAGTATAATCCT GAGATCCATTTGGTGGAATCAGAACTTAAAGCTAGTGAACTGAAAAATGTCCTGGA CGTTATTATGAATGCATTTCACTGGTGTTCTGTCTTTATGACAGAAGAACTTGTCGAC AAAGACAACAACTTTTATGCGGAATTAGAAGAGATTTACGACGAAATTTATCCCGTT ATTTCGTTATATAATTTAGTTCGTAATTACGTGACTCAGAAACCCTACAGCACAAAA AAGATTAAATTAAACTTTGGGATTCCGACTCTTGCTGATGGATGGAGCAAGTCCAAG GAGTACTCTAATAACGCCATTATCTTGATGCGTGACAACCTGTACTACCTGGGCATT TTTAACGCTAAAAACAAACCCGACAAAAAGATCATTGAAGGGAACACCTCGGAAAA TAAGGGGGACTATAAAAAAATGATCTACAATCTGTTGCCAGGCCCAAATAAGATGA TCCCAAAGGTTTTTTTATCTTCCAAAACTGGCGTAGAAACTTACAAGCCGAGCGCAT ACATCCTTGAAGGATATAAACAAAACAAACATATCAAAAGTTCAAAGGACTTCGAT ATTACGTTCTGCCATGATTTAATCGATTATTTCAAGAATTGCATCGCGATTCACCCAG AGTGGAAAAACTTTGGGTTTGATTTTTCAGACACCAGCACTTACGAGGATATTAGTG GATTCTATCGTGAGGTTGAACTGCAGGGCTATAAAATTGACTGGACCTATATTTCTG AAAAAGATATTGATCTGCTTCAGGAGAAAGGCCAATTGTACTTATTTCAAATCTATA ACAAGGATTTCTCCAAGAAGTCCACGGGTAATGACAACTTACACACAATGTATCTGA AGAATCTGTTTAGTGAGGAGAACTTGAAGGACATTGTGCTGAAGCTTAATGGCGAG GCCGAAATCTTTTTTCGTAAGTCCTCCATTAAAAACCCTATTATCCATAAGAAAGGG AGTATTCTTGTCAACCGCACGTATGAGGCCGAAGAAAAGGACCAATTCGGAAACAT CCAAATTGTCCGTAAAAATATTCCTGAGAACATTTACCAGGAGCTTTACAAGTATTT CAACGACAAGAGTGATAAAGAACTTTCAGATGAGGCGGCGAAACTGAAGAATGTAG TGGGGCACCACGAAGCTGCCACGAATATTGTAAAGGATTACCGTTACACCTACGAC AAGTACTTTTTGCATATGCCCATCACAATTAATTTTAAGGCCAATAAAACTGGTTTTA TCAACGATCGTATCTTACAGTACATTGCTAAGGAAAAAGATCTGCACGTTATCGGTA TCGATCGCGGGGAACGCAATCTGATTTATGTTAGTGTGATTGACACGTGCGGAAATA TTGTTGAGCAGAAGAGCTTTAATATCGTAAATGGATATGACTATCAAATTAAACTGA AGCAACAGGAAGGGGCCCGCCAGATTGCCCGCAAGGAGTGGAAAGAAATTGGAAA GATCAAGGAGATTAAAGAAGGGTACCTTTCCCTTGTTATCCACGAAATCTCGAAAAT GGTGATCAAGTACAATGCCATTATTGCTATGGAGGATCTGTCATATGGGTTTAAGAA AGGCCGCTTTAAGGTGGAACGTCAGGTTTACCAGAAGTTTGAGACCATGCTTATCAA TAAGCTGAATTATCTTGTCTTCAAAGACATCTCAATCACAGAGAACGGCGGGCTGTT AAAAGGATATCAGCTGACCTATATCCCCGACAAACTGAAAAATGTCGGGCACCAAT GCGGCTGTATTTTCTACGTGCCCGCTGCATACACATCTAAAATTGACCCAACGACTG GATTCGTAAATATTTTTAAGTTTAAGGATCTTACGGTAGATGCAAAGCGCGAATTTA TCAAGAAATTTGATAGTATCCGTTACGACAGCGAGAAAAACTTATTTTGTTTTACGT TCGATTATAACAACTTCATCACGCAAAATACCGTCATGTCAAAATCTTCCTGGTCAG TCTATACGTATGGCGTCCGTATCAAGCGCCGCTTCGTCAACGGGCGTTTTTCAAACG AGTCAGATACCATCGATATCACCAAAGATATGGAAAAAACATTGGAGATGACGGAC ATCAATTGGCGCGATGGTCATGACTTACGCCAGGACATTATTGACTACGAAATCGTA CAACATATTTTTGAGATTTTCCGTCTGACCGTGCAAATGCGCAACTCATTATCCGAA CTTGAGGATCGTGATTACGACCGCTTGATCAGTCCTGTTCTGAACGAGAATAATATT TTTTACGACAGTGCCAAGGCGGGAGACGCACTGCCCAAGGACGCTGACGCTAACGG AGCTTATTGTATTGCGTTGAAGGGACTTTACGAAATCAAGCAAATCACTGAAAACTG GAAGGAGGATGGTAAATTCTCACGCGACAAGTTGAAAATTTCGAACAAGGACTGGT TCGATTTCATCCAAAACAAGCGTTATTTAAAACGTCCGGCAGCGACCAAAAAAGCC GGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAAGA AACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 68 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAACGGGA CTAATAACTTCCAGAACTTCATCGGTATTTCATCATTACAAAAAACGCTTCGTAACG CCTTGATCCCAACAGAAACGACCCAACAATTTATTGTAAAAAACGGCATCATCAAA GAAGACGAACTGCGTGGCGAAAATCGCCAAATTTTGAAGGACATTATGGATGACTA TTATCGTGGGTTTATCTCGGAGACATTATCCTCCATCGACGACATTGATTGGACGAG TCTTTTTGAGAAAATGGAGATCCAGCTTAAAAATGGTGATAACAAGGATACATTGAT CAAGGAGCAAACCGAGTACCGCAAGGCCATCCATAAGAAGTTCGCAAATGACGACC GCTTCAAAAATATGTTTAGTGCCAAATTGATCTCGGATATCCTTCCTGAGTTCGTAAT TCACAACAATAATTATAGCGCATCCGAAAAGGAGGAAAAGACTCAAGTCATTAAGC TTTTCAGTCGCTTTGCTACCTCGTTTAAGGACTATTTCAAGAACCGCGCGAACTGCTT CTCAGCGGATGACATTTCTTCCTCGTCGTGTCACCGCATCGTGAATGATAATGCGGA GATCTTCTTTAGTAATGCCTTGGTATACCGCCGCATTGTTAAATCCCTGTCTAACGAC GATATCAATAAGATCTCAGGAGATATGAAGGATAGCCTTAAAGAAATGTCTCTGGA AGAAATTTACTCCTATGAAAAGTACGGTGAGTTTATCACCCAAGAGGGGATTAGCTT TTATAACGATATCTGCGGGAAGGTGAATTCGTTTATGAACCTTTATTGTCAAAAGAA TAAGGAGAATAAGAACTTATATAAGCTTCAGAAACTGCATAAACAAATCTTATGCA TTGCCGATACTAGCTATGAAGTTCCGTATAAATTCGAGAGCGATGAAGAAGTTTATC AGAGCGTCAATGGGTTCTTGGATAACATTTCATCAAAACACATCGTGGAACGTCTGC GTAAGATTGGGGATAACTACAACGGATATAATCTTGACAAAATTTATATTGTATCTA AATTCTATGAGTCGGTGAGTCAAAAGACCTACCGTGATTGGGAAACAATCAATACC GCGTTAGAAATCCACTATAACAACATTCTGCCAGGGAATGGTAAAAGTAAAGCGGA CAAAGTCAAGAAGGCTGTGAAGAACGATCTGCAAAAGAGTATTACAGAGATTAACG AATTAGTCTCCAATTATAAGTTATGCTCGGACGATAACATTAAGGCGGAGACGTATA TTCATGAGATTTCGCATATTCTTAACAACTTCGAGGCACAAGAGCTTAAGTATAACC CAGAGATTCACCTTGTCGAATCGGAGCTGAAGGCATCGGAATTAAAAAATGTCTTA GATGTAATCATGAACGCGTTCCATTGGTGCAGTGTTTTCATGACTGAGGAGTTAGTT GACAAGGACAATAACTTCTACGCAGAATTAGAAGAGATCTATGATGAGATTTATCC AGTGATTTCGCTGTATAATCTGGTACGTAATTACGTCACTCAAAAGCCCTACTCAAC AAAAAAAATTAAGCTGAACTTCGGAATTCCGACTCTGGCCGACGGGTGGTCCAAGT CAAAGGAGTATTCTAATAATGCTATCATCCTGATGCGCGATAACTTATACTATTTGG GAATTTTCAATGCCAAAAATAAACCAGATAAAAAGATTATCGAAGGTAATACAAGC GAGAATAAGGGTGACTATAAGAAAATGATTTACAATCTTCTTCCAGGCCCTAACAA GATGATTCCCAAAGTTTTTTTGTCCAGTAAAACAGGGGTCGAAACTTACAAGCCCAG TGCCTATATCCTTGAAGGGTACAAGCAGAATAAGCACATCAAATCCTCGAAAGACTT TGATATTACATTTTGTCATGACTTAATCGATTATTTTAAGAACTGTATCGCAATCCAT CCAGAATGGAAGAACTTCGGGTTTGATTTCTCTGATACTTCCACGTATGAGGATATT TCCGGGTTCTACCGCGAAGTAGAGCTTCAGGGCTATAAAATTGACTGGACATATATT TCAGAAAAAGACATCGATCTGTTACAAGAAAAAGGACAGTTGTATCTGTTTCAAATC TATAATAAGGATTTCTCCAAAAAGTCAACTGGAAATGATAACTTACATACAATGTAT CTGAAAAATCTTTTTAGTGAAGAGAATTTGAAGGATATCGTGCTGAAGTTAAATGGC GAAGCAGAGATCTTCTTCCGCAAGTCCTCGATCAAGAATCCTATCATCCACAAGAAA GGTAGTATTCTGGTTAACCGCACGTACGAGGCCGAGGAAAAAGACCAGTTCGGTAA TATCCAGATTGTACGTAAGAATATTCCTGAAAATATTTACCAGGAATTATACAAGTA TTTTAACGACAAATCGGATAAGGAGCTTTCAGATGAGGCCGCAAAGTTGAAGAACG TCGTAGGACACCATGAGGCCGCTACGAATATCGTCAAGGACTACCGCTATACGTATG ACAAGTACTTCCTGCACATGCCTATTACTATCAATTTCAAAGCTAATAAAACAGGAT TCATCAATGATCGTATCCTTCAGTACATTGCCAAAGAAAAAGATCTGCACGTAATCG GAATCGACCGTGGCGAACGTAATCTGATTTACGTATCAGTTATCGACACATGTGGTA ACATCGTGGAGCAGAAATCTTTTAACATTGTTAACGGCTATGATTATCAGATTAAGC TTAAACAGCAGGAGGGGGCACGCCAAATCGCTCGTAAAGAATGGAAGGAGATTGG AAAGATTAAAGAGATTAAAGAGGGGTACCTTTCGCTGGTTATTCACGAAATTTCCAA GATGGTGATTAAGTACAATGCAATCATCGCGATGGAAGATCTTAGTTACGGATTCAA AAAGGGACGCTTCAAAGTTGAGCGTCAGGTCTACCAGAAATTTGAAACGATGCTGA TTAACAAATTGAATTACTTGGTATTCAAAGATATCTCAATTACTGAAAATGGTGGCT TATTAAAGGGTTACCAGCTTACCTATATCCCGGATAAGCTGAAGAACGTGGGCCATC AATGCGGCTGCATCTTTTACGTCCCTGCCGCATATACCTCTAAAATTGACCCCACCA CCGGATTCGTAAATATTTTTAAATTCAAGGACCTGACGGTGGACGCCAAGCGCGAAT TCATCAAAAAATTCGACTCAATCCGCTATGATTCCGAAAAAAATCTTTTCTGCTTTAC GTTCGATTATAATAACTTCATTACCCAAAACACGGTGATGTCAAAATCGTCCTGGAG CGTGTATACTTATGGAGTGCGTATCAAGCGCCGCTTTGTTAATGGGCGCTTCAGTAA CGAAAGCGATACCATCGACATTACCAAAGACATGGAGAAGACGCTTGAAATGACGG ATATCAATTGGCGTGACGGACACGATCTTCGTCAGGATATCATCGACTACGAGATTG TGCAACATATCTTTGAGATTTTCCGTTTAACTGTTCAAATGCGTAACTCCTTGTCCGA ATTGGAAGACCGTGATTACGACCGCTTGATTTCACCAGTGCTTAACGAGAATAACAT CTTCTACGACTCCGCCAAAGCAGGCGATGCCCTGCCAAAGGACGCTGATGCAAATG GTGCATACTGTATCGCGTTGAAGGGCTTATACGAGATTAAGCAAATCACCGAAAATT GGAAAGAGGATGGAAAGTTCAGTCGCGATAAGCTGAAGATCTCTAATAAAGATTGG TTTGACTTTATCCAGAACAAACGTTATTTAAAACGTCCGGCAGCGACCAAAAAAGCC GGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAAGA AACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 69 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAACGGTA CCAATAATTTCCAAAATTTCATCGGAATCTCATCCTTGCAAAAAACCTTGCGCAATG CTTTGATCCCCACCGAAACCACGCAGCAGTTCATCGTGAAAAACGGCATTATCAAAG AGGATGAGTTGCGCGGGGAAAACCGTCAAATTCTTAAGGATATCATGGACGATTAC TACCGTGGGTTTATCAGTGAGACCCTGTCAAGCATTGACGACATTGACTGGACCAGC TTATTTGAGAAGATGGAGATTCAATTAAAGAACGGGGACAATAAGGACACGCTTAT CAAAGAGCAGACAGAATACCGTAAAGCGATTCATAAGAAATTTGCAAATGACGATC GCTTCAAGAACATGTTTTCAGCAAAATTAATCAGCGACATCCTTCCCGAATTTGTGA TTCATAATAACAACTATTCGGCTAGCGAAAAAGAGGAGAAAACTCAGGTTATTAAG CTTTTCTCGCGTTTTGCCACTTCGTTCAAAGACTATTTTAAGAATCGCGCAAACTGCT TTTCGGCTGATGATATTTCCAGTTCTAGCTGCCATCGTATCGTTAACGATAATGCTGA GATTTTCTTCTCTAATGCCCTGGTGTATCGTCGTATCGTTAAATCTTTGAGCAACGAC GATATTAATAAGATTTCAGGCGACATGAAGGATTCTTTAAAGGAGATGTCTTTAGAA GAGATTTATTCCTATGAGAAATATGGCGAGTTTATCACCCAAGAAGGAATTTCGTTC TACAACGACATCTGTGGCAAAGTGAACAGCTTCATGAATTTATACTGCCAAAAGAAT AAGGAGAATAAAAATTTATATAAACTGCAGAAACTGCATAAGCAAATTCTTTGCATT GCAGACACCTCTTATGAAGTTCCTTATAAGTTTGAATCGGACGAGGAGGTATATCAG AGTGTGAACGGGTTCCTGGACAATATTTCATCCAAGCATATTGTTGAACGTTTACGC AAAATTGGAGACAATTACAATGGGTATAACCTTGACAAAATTTACATCGTGTCGAA GTTTTACGAATCGGTAAGCCAGAAGACCTATCGTGACTGGGAAACTATCAATACCGC CTTAGAAATTCATTACAACAATATTCTTCCTGGTAACGGCAAAAGCAAAGCCGATAA GGTAAAGAAGGCTGTCAAGAACGACCTGCAAAAGTCTATCACAGAGATCAACGAGT TAGTCTCTAACTACAAATTATGTTCCGACGACAATATTAAAGCCGAAACCTACATCC ATGAGATCTCACACATTCTTAACAATTTTGAGGCCCAGGAGCTGAAATATAACCCAG AAATTCACCTTGTAGAGAGCGAATTAAAAGCCTCCGAGCTGAAGAACGTTTTGGAT GTAATCATGAACGCATTTCATTGGTGCAGCGTATTTATGACAGAGGAGTTGGTCGAC AAGGACAATAACTTTTACGCCGAGCTTGAAGAAATCTACGATGAAATTTACCCGGTA ATTAGTTTATATAATTTAGTTCGCAACTACGTAACTCAGAAACCCTACAGTACCAAG AAGATTAAATTGAACTTTGGGATCCCGACACTTGCTGACGGTTGGAGTAAATCAAAA GAATACTCCAATAATGCAATTATCCTGATGCGCGACAATCTTTACTACTTGGGGATC TTTAACGCAAAGAACAAACCAGATAAGAAAATCATCGAGGGCAACACCAGCGAGA ATAAAGGCGATTACAAGAAAATGATCTATAATCTTTTGCCGGGACCGAACAAAATG ATCCCAAAGGTTTTCCTGTCGTCGAAAACGGGAGTCGAGACATATAAACCATCTGCG TACATCTTGGAAGGTTACAAACAGAATAAGCATATTAAGTCTAGTAAAGACTTCGAC ATCACCTTTTGTCATGACCTGATTGATTATTTCAAGAACTGTATTGCTATCCATCCAG AATGGAAAAACTTCGGATTTGACTTCTCCGATACTAGCACCTACGAAGACATTTCGG GTTTTTATCGCGAAGTAGAGCTTCAAGGGTACAAAATTGATTGGACATATATTAGCG AGAAAGACATTGATTTGCTTCAAGAGAAGGGACAGTTATATTTATTCCAGATCTACA ACAAAGACTTCTCGAAGAAATCCACCGGTAATGATAATCTTCACACTATGTACCTGA AGAATTTATTTTCAGAGGAAAATCTGAAGGACATTGTACTTAAACTTAATGGAGAAG CCGAAATCTTCTTCCGCAAGAGTTCCATTAAAAATCCGATTATTCATAAAAAGGGAA GTATCCTTGTGAACCGCACGTATGAGGCCGAAGAGAAGGATCAGTTTGGGAATATT CAAATTGTCCGCAAAAACATCCCCGAGAACATCTACCAGGAACTGTATAAATACTTT AATGATAAATCTGATAAAGAGTTATCAGACGAGGCTGCCAAACTGAAAAACGTAGT CGGTCATCATGAGGCAGCGACCAATATTGTAAAGGACTACCGTTACACCTACGACA AGTATTTCCTTCACATGCCGATCACGATTAATTTTAAGGCTAACAAGACCGGCTTTA TCAATGACCGCATCTTGCAGTACATCGCGAAAGAGAAAGATTTACACGTCATCGGA ATTGATCGTGGAGAGCGTAATCTTATCTACGTCAGCGTCATCGACACCTGTGGAAAC ATTGTGGAACAAAAAAGTTTTAATATCGTAAACGGCTACGACTATCAAATTAAACTT AAACAGCAAGAGGGAGCTCGCCAGATCGCTCGCAAAGAGTGGAAAGAGATTGGGA AAATTAAAGAAATTAAAGAGGGTTACCTGTCGCTGGTAATTCACGAAATCTCGAAA ATGGTCATCAAATATAATGCAATTATCGCTATGGAGGATCTGTCCTACGGGTTCAAG AAGGGACGTTTTAAAGTAGAGCGCCAGGTGTATCAAAAATTCGAAACCATGTTGAT CAATAAGCTTAACTATTTGGTCTTCAAAGATATTTCGATTACGGAGAACGGAGGTTT GTTGAAAGGATATCAGCTGACGTATATCCCAGACAAGTTGAAAAACGTGGGGCATC AATGTGGATGTATTTTCTATGTGCCCGCGGCCTACACGAGTAAGATCGATCCTACCA CTGGTTTCGTCAACATTTTCAAATTTAAAGATCTTACCGTGGATGCGAAGCGCGAAT TTATTAAGAAATTTGATAGCATTCGCTATGATTCCGAAAAGAACCTGTTCTGTTTTAC GTTCGACTATAACAATTTCATTACCCAAAACACGGTGATGAGCAAATCCTCTTGGTC AGTTTATACATACGGTGTACGTATCAAACGCCGTTTCGTTAACGGACGCTTTTCCAA TGAGTCTGATACAATCGATATCACGAAAGATATGGAAAAAACATTAGAGATGACTG ATATCAACTGGCGTGACGGGCACGACCTGCGTCAAGACATTATTGACTACGAGATTG TGCAGCATATCTTCGAAATCTTTCGCTTAACTGTGCAAATGCGTAACTCGTTATCCGA GTTAGAAGACCGTGACTACGATCGCCTGATTTCACCCGTCTTGAACGAAAATAACAT CTTCTACGATTCCGCGAAGGCTGGGGACGCATTGCCCAAGGACGCAGACGCGAATG GAGCGTACTGTATTGCGCTTAAAGGATTATATGAAATCAAGCAGATCACCGAAAATT GGAAGGAGGACGGGAAGTTCTCACGCGACAAACTGAAGATTTCAAATAAGGACTGG TTCGATTTCATTCAGAATAAGCGTTACCTGAAACGTCCGGCAGCGACCAAAAAAGCC GGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAAGA AACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 70 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAATAATGGTA CGAACAACTTTCAGAACTTCATCGGCATCTCCAGCCTTCAAAAGACTTTACGCAACG CATTGATTCCCACGGAGACTACGCAACAGTTTATCGTAAAAAATGGTATTATCAAAG AAGATGAATTACGCGGGGAGAATCGCCAGATTCTTAAGGACATTATGGACGATTAT TACCGTGGATTCATCAGTGAGACACTGAGCTCCATTGATGACATCGACTGGACGTCA TTGTTTGAAAAGATGGAAATCCAGTTGAAAAATGGCGATAACAAAGATACATTGAT TAAAGAGCAGACAGAGTACCGCAAAGCAATTCACAAGAAATTCGCCAATGATGATC GTTTTAAGAACATGTTTAGTGCCAAGCTTATTTCGGATATCTTACCCGAATTCGTGAT TCACAACAACAATTATTCGGCAAGTGAGAAAGAGGAAAAGACCCAGGTTATCAAAT TGTTTTCGCGCTTCGCCACTTCGTTCAAAGATTATTTCAAGAACCGTGCAAACTGTTT CTCCGCTGACGACATCAGTTCCAGCTCATGCCACCGTATTGTAAATGACAATGCGGA GATCTTTTTCAGTAATGCCTTAGTATATCGTCGCATTGTAAAGAGCTTATCTAATGAT GACATTAACAAGATCTCGGGTGATATGAAGGACTCACTTAAGGAGATGAGTCTGGA AGAGATCTACTCCTACGAAAAATACGGGGAATTCATCACCCAGGAGGGAATTTCAT TCTACAACGATATCTGCGGCAAAGTTAACTCCTTTATGAATCTGTACTGTCAAAAGA ACAAGGAGAATAAAAACCTGTATAAATTGCAGAAACTTCATAAACAAATTTTGTGT ATCGCAGACACGAGTTATGAAGTACCTTATAAATTCGAATCCGACGAAGAGGTATA TCAGTCCGTAAATGGGTTCCTGGACAATATCAGTAGTAAGCACATTGTGGAACGCTT ACGCAAAATTGGAGACAATTACAACGGGTATAACCTGGACAAAATCTACATCGTAT CCAAATTTTATGAAAGCGTGTCTCAAAAAACTTATCGTGATTGGGAAACAATCAACA CGGCTCTTGAGATCCATTACAATAACATCTTGCCGGGTAACGGCAAATCGAAGGCA GACAAAGTTAAAAAAGCAGTTAAGAACGACTTACAGAAAAGCATTACGGAGATTAA CGAGTTAGTAAGTAATTACAAATTATGCTCCGACGATAATATCAAAGCTGAAACCTA CATCCATGAAATTAGCCACATTTTGAACAATTTCGAAGCGCAGGAGCTGAAATATAA CCCTGAAATCCATCTGGTAGAGTCTGAGTTGAAGGCGTCAGAACTGAAAAACGTTCT TGACGTCATCATGAATGCCTTTCACTGGTGTAGTGTTTTTATGACTGAGGAGCTTGTA GATAAGGACAACAACTTCTATGCTGAACTTGAAGAGATCTACGATGAAATCTACCCC GTAATCAGTCTGTATAATTTAGTTCGTAACTACGTCACGCAGAAACCCTATTCGACT AAGAAAATTAAGCTGAACTTTGGGATCCCTACTTTGGCAGACGGGTGGAGCAAGAG TAAAGAATACAGTAATAATGCAATTATCTTGATGCGCGATAACTTATATTACTTAGG TATTTTCAATGCTAAGAACAAACCTGATAAGAAGATTATCGAAGGAAATACGAGTG AGAATAAGGGAGACTACAAAAAGATGATTTACAACTTGCTGCCAGGGCCTAATAAG ATGATTCCAAAAGTTTTTCTGTCGAGCAAGACAGGGGTTGAAACTTATAAGCCATCC GCTTATATCCTTGAGGGGTACAAGCAGAATAAGCATATCAAGTCCTCCAAAGATTTT GATATTACATTTTGCCACGACTTAATTGATTACTTCAAGAACTGCATCGCAATCCATC CCGAATGGAAGAATTTCGGCTTCGATTTCTCAGATACGTCCACGTATGAGGATATCT CAGGCTTTTACCGCGAAGTTGAGCTGCAAGGTTATAAAATTGATTGGACATACATCT CCGAAAAAGACATTGATCTTTTACAGGAAAAGGGCCAATTATACTTATTTCAAATCT ATAACAAAGATTTTAGCAAGAAGTCCACAGGTAATGATAACCTGCATACGATGTATT TGAAAAATCTTTTCAGTGAAGAGAATTTGAAGGATATCGTCCTGAAGCTGAACGGTG AGGCTGAGATCTTCTTCCGCAAATCGTCTATCAAAAACCCCATCATTCACAAAAAGG GAAGTATCTTAGTAAACCGCACTTATGAAGCGGAGGAAAAGGATCAGTTCGGGAAC ATCCAGATCGTGCGCAAGAACATTCCAGAAAACATCTATCAGGAACTTTACAAATAT TTCAATGACAAGTCTGATAAAGAATTATCAGACGAGGCGGCGAAACTTAAAAATGT TGTTGGACACCACGAAGCAGCGACGAATATTGTAAAGGATTATCGCTACACATACG ATAAATACTTTTTGCACATGCCAATCACCATTAACTTTAAGGCGAACAAGACAGGTT TCATTAACGACCGTATTCTGCAATATATCGCAAAGGAAAAAGACCTGCACGTTATTG GGATCGATCGTGGCGAACGCAATTTGATCTACGTAAGCGTTATCGACACTTGCGGAA ATATCGTTGAACAAAAAAGCTTTAATATCGTCAATGGATACGATTACCAAATCAAGC TGAAACAACAAGAAGGGGCACGTCAGATCGCTCGTAAAGAATGGAAAGAGATTGGT AAGATCAAAGAGATTAAAGAAGGGTATCTTTCTTTAGTAATTCACGAGATTTCGAAA ATGGTTATTAAATACAATGCGATTATTGCTATGGAAGACTTAAGCTACGGCTTTAAG AAAGGTCGCTTCAAAGTGGAGCGCCAAGTGTATCAGAAGTTTGAAACGATGTTGAT TAACAAATTAAATTACCTGGTCTTTAAGGACATCAGTATCACAGAAAATGGGGGGTT GCTTAAAGGGTACCAGCTTACATACATCCCTGATAAACTGAAAAATGTCGGTCATCA GTGCGGATGTATCTTCTATGTACCAGCAGCCTATACCAGTAAGATTGACCCTACTAC TGGCTTTGTGAATATTTTTAAATTCAAGGATTTAACCGTGGACGCCAAGCGTGAATT TATTAAAAAATTTGATTCGATTCGCTACGACAGTGAGAAAAACCTTTTCTGCTTTAC CTTTGACTACAACAATTTTATTACCCAGAACACCGTAATGTCAAAGAGTTCGTGGTC TGTATATACCTACGGTGTTCGCATCAAGCGCCGCTTCGTAAACGGGCGTTTCAGTAA CGAATCTGACACCATCGACATCACTAAAGATATGGAGAAGACATTGGAAATGACGG ACATTAATTGGCGTGATGGCCATGACTTACGTCAGGACATTATTGATTACGAAATTG TGCAGCATATCTTCGAGATTTTCCGTTTGACAGTTCAGATGCGCAACTCACTGAGTG AGTTAGAAGATCGCGATTACGACCGTCTGATCTCACCGGTCCTTAATGAAAACAACA TTTTCTACGACTCAGCAAAGGCGGGTGATGCCCTGCCAAAGGATGCGGACGCTAAT GGCGCCTACTGCATCGCCCTGAAAGGATTGTATGAAATTAAGCAGATTACAGAAAA TTGGAAGGAAGATGGTAAATTTAGCCGTGATAAATTAAAAATCTCGAACAAGGATT GGTTCGATTTTATTCAGAACAAACGTTATTTGAAACGTCCGGCAGCGACCAAAAAAG CCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAA GAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 71 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAATGGAA CAAATAATTTTCAAAATTTTATCGGCATCTCAAGTCTTCAAAAAACCCTTCGCAATG CCCTGATTCCAACTGAAACAACCCAGCAATTTATCGTCAAGAACGGCATCATTAAGG AAGACGAGTTACGCGGGGAGAACCGTCAAATCCTGAAAGATATCATGGATGACTAC TATCGTGGGTTCATTTCGGAAACCTTGTCTTCAATCGACGACATTGACTGGACGAGT CTTTTCGAGAAAATGGAAATTCAGCTTAAAAATGGAGACAACAAGGATACTCTGAT TAAGGAACAGACAGAATATCGCAAAGCTATCCACAAAAAGTTCGCTAATGATGATC GTTTCAAAAATATGTTTTCTGCTAAATTGATTTCCGATATCTTGCCTGAATTTGTAAT CCACAACAACAATTATTCTGCTTCCGAGAAGGAAGAGAAGACCCAGGTCATTAAAT TATTCAGCCGCTTTGCAACCAGCTTTAAAGACTACTTTAAGAATCGCGCTAACTGCT TTTCGGCGGATGACATCTCATCATCATCATGCCACCGCATTGTGAACGACAATGCGG AGATCTTCTTTTCGAATGCGTTAGTTTATCGTCGCATTGTCAAAAGTCTTAGCAATGA TGACATCAACAAGATCTCAGGAGACATGAAAGATTCCTTAAAGGAGATGTCTCTTG AGGAAATCTATTCGTATGAGAAATACGGCGAGTTCATTACCCAGGAAGGTATTAGTT TCTACAATGATATCTGCGGCAAAGTAAATTCTTTTATGAATCTGTATTGCCAAAAAA ACAAAGAAAACAAGAATCTTTATAAGTTACAAAAGTTACATAAGCAAATTCTGTGC ATCGCTGATACATCTTATGAGGTACCCTACAAATTTGAAAGTGATGAGGAGGTCTAT CAGAGTGTCAACGGCTTCTTAGACAACATCTCTTCCAAACATATCGTGGAACGCCTG CGTAAAATCGGAGATAACTACAACGGATATAACTTAGATAAAATCTACATCGTGTCC AAGTTTTATGAAAGTGTGAGCCAAAAAACATATCGTGACTGGGAAACCATTAACAC CGCATTGGAAATTCACTATAACAACATTTTGCCAGGCAACGGGAAAAGTAAGGCGG ACAAAGTTAAGAAAGCAGTTAAAAATGACCTGCAAAAAAGCATCACTGAAATTAAC GAATTGGTATCGAATTACAAATTATGTAGCGACGATAATATCAAAGCAGAAACTTA CATTCACGAGATTAGTCACATTTTAAATAACTTCGAGGCCCAGGAATTGAAATACAA TCCCGAAATTCATTTGGTTGAATCAGAACTGAAAGCATCAGAGTTGAAAAATGTGTT AGATGTCATTATGAATGCGTTTCATTGGTGCTCTGTGTTCATGACCGAGGAACTGGT TGATAAAGATAACAACTTTTACGCTGAATTGGAGGAGATTTACGATGAGATTTACCC GGTCATTTCGCTTTATAACTTAGTGCGCAATTATGTGACGCAGAAACCATATTCCAC GAAGAAAATCAAACTTAATTTTGGCATCCCTACTCTGGCTGATGGTTGGTCGAAATC GAAAGAGTACAGCAACAACGCGATCATTCTTATGCGTGACAATCTTTACTATTTGGG CATTTTTAATGCCAAGAATAAGCCAGATAAGAAAATCATTGAGGGGAATACTTCCG AGAATAAGGGGGATTACAAAAAGATGATCTATAACTTGCTGCCCGGCCCCAACAAA ATGATTCCTAAGGTTTTCTTGTCAAGCAAGACGGGCGTCGAAACATATAAGCCGTCA GCTTATATTCTGGAAGGCTATAAACAGAATAAGCACATCAAGTCTTCCAAGGACTTT GACATCACTTTTTGCCACGATTTGATCGACTACTTTAAGAACTGTATTGCGATTCATC CGGAATGGAAGAACTTCGGTTTCGACTTTTCCGATACCTCAACATACGAGGATATCA GCGGCTTCTACCGTGAAGTCGAGCTTCAAGGCTACAAGATCGATTGGACATATATTT CAGAGAAGGACATTGATTTGTTACAAGAGAAAGGTCAACTTTACTTATTTCAGATCT ATAACAAAGACTTTTCGAAGAAATCGACAGGAAACGATAACTTACACACTATGTAT TTAAAAAATCTGTTTTCGGAGGAAAACCTGAAAGATATTGTGCTGAAACTTAACGGC GAGGCAGAGATCTTTTTCCGTAAAAGCTCAATCAAGAATCCTATCATCCATAAAAAA GGTAGTATTCTTGTCAACCGCACATATGAAGCGGAGGAGAAGGACCAATTCGGAAA CATCCAAATTGTCCGTAAGAATATTCCGGAGAACATTTACCAAGAGTTGTATAAATA CTTTAACGATAAGTCAGATAAGGAACTTAGCGATGAGGCGGCGAAGCTTAAAAACG TAGTTGGGCATCATGAAGCTGCTACCAACATTGTAAAAGATTACCGTTACACCTATG ACAAGTATTTCTTGCACATGCCCATTACGATCAATTTCAAAGCAAATAAGACAGGCT TTATCAATGATCGCATCCTGCAGTACATTGCTAAAGAGAAGGATTTGCATGTTATCG GTATTGATCGCGGAGAGCGCAATTTGATCTACGTCTCCGTAATCGACACTTGCGGTA ACATTGTTGAGCAGAAGTCGTTCAACATCGTTAATGGTTATGATTACCAAATCAAGC TGAAGCAGCAAGAGGGTGCCCGCCAGATCGCGCGTAAGGAATGGAAAGAAATCGG GAAAATTAAAGAGATCAAAGAAGGCTATTTGTCTCTGGTAATTCACGAAATCAGCA AGATGGTGATCAAGTATAACGCGATCATTGCGATGGAGGATCTTTCTTATGGCTTCA AGAAAGGGCGCTTTAAAGTCGAACGCCAGGTCTACCAGAAATTTGAGACAATGCTT ATCAACAAGCTTAACTATCTTGTATTTAAGGATATTTCCATCACTGAGAACGGAGGA CTTTTAAAGGGGTACCAACTGACGTACATTCCTGATAAGCTGAAGAACGTTGGTCAT CAATGCGGATGCATCTTCTATGTGCCAGCGGCTTACACCTCCAAAATCGATCCCACT ACAGGCTTTGTCAATATCTTCAAATTCAAGGATTTGACCGTTGACGCGAAGCGCGAG TTTATCAAGAAGTTTGATAGCATTCGCTACGACAGCGAAAAAAATTTATTTTGTTTT ACTTTCGACTACAATAACTTTATTACTCAGAACACTGTCATGTCAAAGAGTTCGTGG AGTGTCTACACGTACGGAGTACGTATTAAGCGCCGTTTCGTCAACGGACGCTTCTCA AACGAAAGCGACACGATCGACATCACCAAAGACATGGAAAAAACTCTTGAGATGAC GGATATCAATTGGCGCGACGGCCATGACCTGCGTCAGGATATCATTGATTACGAGAT CGTTCAGCACATCTTCGAAATCTTCCGCCTTACCGTCCAGATGCGCAACAGTTTAAG CGAGCTTGAAGACCGCGACTACGATCGTTTGATTAGCCCCGTTCTGAACGAGAATAA TATTTTCTACGACAGCGCAAAGGCCGGTGATGCTTTGCCAAAGGACGCAGACGCGA ATGGAGCCTACTGCATCGCCCTGAAGGGCTTATATGAGATTAAGCAAATTACCGAA AATTGGAAGGAAGATGGTAAGTTCTCCCGTGATAAGCTTAAAATTAGCAATAAGGA TTGGTTCGACTTCATCCAGAACAAACGTTACCTGAAACGTCCGGCAGCGACCAAAA AAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAA AAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 72 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAACGGAA CAAACAATTTCCAAAACTTCATCGGTATCTCTTCGTTGCAGAAGACTCTGCGTAATG CTTTGATCCCGACGGAGACAACCCAACAATTTATCGTCAAAAACGGTATTATTAAGG AGGACGAGTTACGTGGAGAAAATCGTCAAATCCTTAAGGACATCATGGACGATTAT TATCGCGGGTTTATTTCTGAAACCCTGAGCAGTATCGATGATATCGACTGGACCTCA CTTTTTGAGAAAATGGAGATCCAGTTGAAGAACGGTGATAACAAAGACACTCTGAT CAAAGAGCAAACTGAATACCGCAAGGCAATTCACAAAAAGTTCGCCAACGACGACC GTTTCAAGAATATGTTCTCAGCTAAGTTAATCAGCGACATTTTGCCAGAGTTCGTTAT CCACAACAATAATTATAGTGCTTCAGAGAAGGAGGAAAAAACCCAAGTGATTAAAC TTTTTTCGCGCTTTGCAACCTCATTCAAGGACTACTTCAAGAATCGCGCGAATTGCTT CAGTGCGGACGACATTTCTTCTTCAAGTTGCCATCGTATCGTTAACGATAACGCGGA AATTTTCTTCTCTAATGCTTTGGTGTATCGCCGCATTGTAAAATCGCTTAGTAACGAT GACATTAATAAGATCTCAGGTGATATGAAAGATTCATTGAAGGAAATGAGCTTGGA AGAGATTTACAGTTACGAAAAATATGGAGAATTTATTACTCAGGAAGGCATCTCATT CTATAACGATATCTGCGGGAAGGTAAATTCGTTTATGAACTTATATTGCCAGAAAAA TAAAGAGAATAAAAATTTGTATAAGCTTCAGAAGTTGCACAAACAGATCCTGTGCA TTGCAGACACCTCGTATGAGGTTCCGTATAAATTTGAGTCCGATGAAGAAGTGTATC AGTCTGTGAATGGTTTCTTAGATAATATCTCTTCCAAGCATATTGTCGAACGCCTGCG CAAAATTGGTGATAACTATAACGGATACAATCTGGATAAAATTTACATCGTTTCTAA ATTTTACGAGTCAGTCTCGCAGAAGACCTACCGCGACTGGGAAACAATTAACACGG CATTGGAGATTCACTACAATAATATCTTGCCTGGTAACGGTAAGTCTAAGGCAGATA AGGTAAAAAAAGCTGTGAAAAACGACCTTCAGAAAAGCATCACGGAGATTAATGAG CTGGTGAGTAATTACAAATTATGTTCAGACGATAATATTAAAGCTGAAACGTATATC CATGAAATCTCGCATATCTTGAACAACTTCGAGGCCCAAGAACTTAAATATAACCCC GAAATCCATTTAGTCGAGTCTGAATTGAAAGCGTCGGAATTAAAAAACGTCTTAGAC GTCATTATGAACGCGTTTCACTGGTGTTCAGTTTTCATGACCGAAGAGCTGGTCGAC AAAGACAACAACTTCTATGCGGAATTGGAGGAAATCTATGATGAAATCTACCCTGTT ATTTCACTGTATAACCTTGTGCGCAACTATGTCACTCAGAAGCCGTATTCGACCAAA AAAATTAAATTGAATTTCGGTATCCCTACTCTTGCAGACGGATGGAGTAAAAGCAAG GAATACAGTAATAACGCCATTATTCTTATGCGCGACAATTTATACTACCTGGGCATC TTTAACGCAAAGAATAAGCCGGATAAGAAGATTATTGAGGGTAACACCAGTGAGAA CAAGGGCGACTATAAGAAGATGATCTATAACTTATTGCCAGGTCCAAATAAAATGA TCCCAAAAGTATTCTTATCATCAAAGACGGGAGTTGAAACCTATAAGCCTAGTGCCT ATATTCTTGAGGGATATAAACAGAACAAGCACATTAAGTCGTCTAAGGATTTTGACA TTACGTTCTGCCATGACTTAATCGACTATTTTAAAAACTGTATTGCGATTCACCCCGA ATGGAAGAATTTTGGATTCGATTTTTCGGATACCTCGACCTATGAAGATATTTCGGG ATTTTATCGTGAAGTGGAGTTGCAAGGCTATAAAATCGATTGGACCTATATCTCAGA AAAAGACATTGATTTATTACAGGAAAAGGGACAACTGTACCTTTTCCAAATTTATAA CAAGGACTTTTCTAAAAAGTCCACAGGAAATGATAACCTTCACACCATGTACCTGAA GAACCTTTTCTCAGAGGAAAACCTGAAGGACATTGTCCTTAAGTTAAATGGAGAAG CGGAGATCTTTTTCCGTAAATCTAGTATCAAGAATCCGATTATCCATAAAAAAGGTT CGATTTTGGTAAATCGCACCTATGAAGCGGAAGAGAAAGATCAATTTGGTAACATC CAGATCGTGCGCAAGAATATCCCGGAGAACATTTACCAAGAGCTGTATAAGTACTTC AATGATAAGTCTGATAAGGAACTGTCAGATGAAGCTGCGAAATTGAAGAACGTGGT TGGGCATCATGAAGCCGCTACCAATATCGTCAAGGATTACCGTTATACCTATGACAA ATATTTCTTACACATGCCGATTACGATCAATTTTAAGGCAAACAAGACAGGATTCAT CAACGACCGTATCTTGCAGTATATTGCCAAAGAGAAGGATCTGCATGTGATCGGTAT TGACCGCGGGGAGCGCAATTTAATCTATGTATCGGTGATCGATACTTGTGGTAACAT CGTAGAACAAAAGAGCTTTAACATCGTGAATGGTTACGACTATCAGATCAAGCTGA AACAACAGGAAGGAGCCCGCCAGATCGCTCGCAAGGAATGGAAAGAAATCGGGAA AATTAAGGAAATCAAGGAAGGCTACCTTTCATTGGTCATTCACGAAATTTCGAAAAT GGTAATTAAGTACAACGCGATCATCGCCATGGAGGACCTTTCGTACGGATTTAAGAA GGGTCGTTTCAAAGTTGAGCGCCAGGTATACCAAAAATTCGAGACTATGCTTATCAA CAAACTTAACTACTTGGTCTTTAAGGACATTTCTATTACCGAAAACGGCGGCTTACT TAAAGGCTATCAATTGACATATATTCCCGACAAACTGAAGAATGTTGGACATCAATG CGGGTGTATTTTCTATGTGCCGGCAGCTTACACTAGTAAGATCGACCCTACAACCGG GTTCGTAAACATTTTTAAATTCAAAGACTTAACAGTCGATGCGAAGCGTGAATTTAT TAAGAAGTTTGATAGTATCCGCTATGACAGTGAAAAGAACTTGTTTTGCTTTACGTT CGACTACAATAACTTTATTACACAGAACACGGTCATGTCTAAATCATCATGGTCGGT TTACACATATGGGGTGCGCATCAAGCGTCGCTTTGTAAATGGCCGTTTTAGTAATGA GAGCGACACAATCGACATCACAAAGGATATGGAGAAAACTCTTGAGATGACAGACA TCAATTGGCGTGACGGTCATGACTTACGCCAAGATATCATCGACTACGAAATCGTAC AGCATATTTTTGAGATTTTTCGTCTTACTGTGCAAATGCGTAATTCTTTATCCGAACT GGAAGATCGTGATTACGACCGCTTGATTAGTCCCGTCTTAAATGAGAACAATATTTT CTATGATTCTGCGAAAGCCGGAGATGCACTGCCCAAAGACGCTGATGCCAATGGCG CGTATTGCATTGCATTAAAAGGATTATATGAGATTAAACAGATTACCGAAAATTGGA AAGAGGACGGTAAATTCTCACGCGATAAATTGAAGATTTCTAACAAGGACTGGTTC GACTTTATCCAAAATAAACGTTATCTTAAACGTCCGGCAGCGACCAAAAAAGCCGG CCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAAGAAA CGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 73 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAATAACGGTA CCAACAACTTTCAGAATTTCATTGGCATTAGCTCGCTTCAAAAAACTTTACGCAATG CTCTTATTCCGACTGAGACGACACAACAGTTTATCGTTAAGAATGGCATCATCAAAG AAGATGAATTACGCGGAGAAAACCGCCAGATCCTGAAAGACATTATGGACGATTAT TACCGTGGGTTCATCTCCGAGACGTTGTCATCGATCGATGACATCGACTGGACGTCA CTTTTTGAAAAAATGGAGATCCAGTTAAAGAACGGTGACAATAAGGATACATTGAT CAAAGAACAGACCGAGTACCGTAAAGCGATTCATAAAAAGTTTGCGAACGATGATC GCTTCAAGAATATGTTTTCTGCGAAATTAATTTCCGACATTTTACCTGAATTTGTTAT TCATAATAACAACTACTCGGCGTCTGAGAAAGAGGAGAAAACCCAAGTGATTAAAC TTTTTTCACGTTTCGCAACGTCGTTCAAAGACTATTTTAAAAATCGTGCTAATTGCTT TAGCGCGGATGACATCAGCTCTAGTTCATGTCATCGCATTGTCAACGATAATGCTGA GATCTTTTTCAGTAATGCGTTAGTGTACCGTCGTATTGTGAAGTCCTTATCTAATGAT GATATCAATAAGATCAGCGGGGATATGAAGGACTCACTTAAGGAGATGAGCTTGGA GGAAATCTATTCCTATGAGAAGTATGGTGAGTTTATTACGCAAGAAGGAATTAGCTT TTACAACGATATCTGTGGAAAGGTGAATTCGTTTATGAATTTGTATTGCCAGAAAAA TAAGGAGAACAAGAACCTTTATAAATTGCAAAAGTTACACAAGCAAATCCTGTGCA TTGCAGATACTTCCTACGAGGTGCCTTACAAGTTTGAATCCGACGAAGAGGTCTACC AATCTGTAAACGGTTTCTTAGATAATATTAGTTCCAAGCATATTGTGGAGCGCCTTC GTAAAATTGGCGATAATTACAACGGTTACAATTTAGACAAAATTTACATTGTCAGTA AATTCTACGAGTCCGTATCTCAAAAGACGTATCGTGATTGGGAGACTATCAATACGG CCCTGGAGATCCACTACAACAATATCTTGCCCGGTAATGGTAAGTCGAAGGCCGATA AAGTTAAGAAAGCGGTGAAAAATGACTTACAGAAGTCAATCACCGAAATTAACGAA TTGGTGTCCAATTATAAATTGTGTTCAGATGATAATATCAAAGCCGAGACCTACATT CATGAGATTTCCCATATCTTAAATAATTTCGAGGCGCAAGAGCTTAAGTATAACCCA GAAATCCACCTGGTAGAATCTGAGTTGAAGGCGTCAGAGTTAAAAAATGTTTTAGAT GTCATTATGAACGCGTTTCACTGGTGCTCCGTATTTATGACGGAGGAATTAGTAGAT AAAGACAACAATTTCTATGCCGAACTTGAGGAAATCTATGATGAGATCTATCCCGTC ATTAGCCTGTATAACTTGGTCCGCAACTATGTTACCCAAAAACCGTACAGTACCAAG AAGATTAAGCTGAATTTCGGCATTCCTACACTGGCTGATGGTTGGAGTAAATCGAAG GAATATTCGAATAACGCGATTATCTTGATGCGCGACAACTTATACTATTTGGGGATC TTTAACGCCAAAAACAAACCGGATAAGAAGATTATTGAGGGAAACACATCAGAGAA CAAAGGCGACTACAAAAAAATGATTTACAACTTGTTACCGGGGCCTAACAAAATGA TCCCGAAGGTGTTCTTATCCAGTAAAACAGGCGTTGAGACCTACAAACCTTCCGCAT ACATCCTGGAAGGGTATAAGCAGAACAAGCACATTAAGTCCAGCAAGGATTTCGAT ATTACCTTCTGTCATGATTTAATTGACTATTTCAAGAACTGTATTGCAATCCACCCCG AGTGGAAGAACTTCGGATTCGACTTCTCAGATACGAGCACATATGAGGACATCTCG GGGTTCTATCGTGAAGTAGAACTGCAGGGATATAAAATTGATTGGACATATATTTCC GAAAAAGACATCGACCTTTTACAAGAGAAGGGTCAACTTTACTTGTTCCAAATTTAC AATAAAGACTTCTCAAAAAAAAGCACGGGTAACGATAATTTACACACTATGTATTTA AAGAACCTTTTCTCGGAAGAGAATTTAAAGGATATCGTATTGAAGTTGAATGGAGA AGCGGAGATCTTCTTCCGTAAGTCCAGTATTAAAAACCCTATTATTCACAAGAAGGG ATCGATTTTAGTTAACCGCACATACGAGGCCGAAGAGAAGGACCAATTTGGGAACA TTCAAATTGTCCGCAAAAACATCCCTGAGAACATTTATCAAGAGCTTTATAAGTACT TTAACGATAAGTCCGATAAGGAATTGTCAGATGAGGCGGCAAAGTTGAAGAATGTC GTGGGGCATCATGAAGCTGCCACCAACATTGTGAAGGACTACCGCTACACTTACGA CAAATACTTCCTGCACATGCCCATTACGATCAATTTTAAGGCCAATAAGACAGGCTT TATTAACGACCGTATTCTTCAATATATCGCTAAGGAGAAGGACCTTCATGTGATTGG GATCGACCGCGGAGAACGTAATTTAATTTATGTGTCCGTCATCGATACGTGTGGAAA TATCGTGGAACAGAAATCATTCAATATCGTGAATGGCTATGATTACCAGATCAAATT AAAACAGCAGGAGGGCGCTCGCCAAATTGCGCGTAAGGAATGGAAAGAGATCGGA AAAATCAAAGAAATCAAAGAAGGATATTTGTCATTGGTGATCCATGAGATTTCAAA AATGGTAATTAAATATAATGCAATTATCGCAATGGAAGACCTGTCCTATGGTTTTAA GAAGGGTCGTTTCAAGGTAGAACGCCAAGTGTATCAAAAGTTCGAGACGATGCTGA TCAATAAGCTGAATTATCTTGTGTTTAAGGACATTAGCATCACGGAAAATGGAGGGC TGTTGAAAGGCTATCAACTGACGTATATCCCTGACAAGCTGAAAAATGTTGGCCATC AGTGCGGGTGCATTTTCTACGTCCCCGCGGCGTATACAAGCAAGATCGATCCTACTA CGGGATTCGTAAATATTTTTAAATTCAAAGACTTAACCGTGGACGCCAAGCGCGAAT TCATTAAGAAGTTTGATAGCATTCGCTACGATTCAGAAAAAAATCTTTTCTGTTTTAC GTTCGATTACAACAATTTTATCACCCAGAACACAGTGATGAGCAAGTCATCCTGGTC TGTCTATACCTACGGTGTCCGTATCAAACGCCGCTTCGTCAACGGACGCTTCTCTAAT GAATCTGATACCATTGACATCACCAAGGACATGGAAAAGACACTTGAGATGACAGA TATTAACTGGCGTGACGGACATGACCTGCGTCAGGACATCATCGATTATGAGATTGT TCAGCATATCTTCGAGATCTTCCGCCTGACAGTACAAATGCGCAATTCACTGTCAGA ACTTGAAGACCGCGACTATGACCGCCTGATCTCTCCAGTATTAAATGAGAACAATAT CTTTTATGACAGTGCTAAGGCCGGCGATGCCCTTCCGAAAGATGCTGATGCTAACGG AGCTTATTGTATTGCATTAAAGGGTCTTTATGAGATCAAGCAAATTACCGAGAATTG GAAGGAGGATGGCAAATTCTCGCGCGACAAACTGAAAATCAGTAACAAGGACTGGT TCGATTTTATTCAGAATAAACGTTACCTGAAACGTCCGGCAGCGACCAAAAAAGCC GGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAAGA AACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 74 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAATAACGGAA CGAACAACTTCCAGAACTTCATCGGCATCAGTTCTTTACAAAAAACCCTGCGTAACG CCCTTATTCCGACTGAGACAACACAACAGTTCATCGTTAAAAACGGAATTATCAAAG AGGACGAGTTGCGCGGCGAGAATCGCCAAATTTTGAAAGATATTATGGACGACTAT TATCGTGGTTTTATTTCAGAAACACTGAGTTCGATTGACGATATCGATTGGACGAGC CTGTTTGAGAAAATGGAAATCCAGTTGAAAAATGGCGATAATAAAGACACTTTAAT CAAAGAACAAACCGAGTATCGTAAAGCGATCCATAAAAAGTTCGCTAATGACGATC GTTTTAAGAATATGTTCAGTGCGAAACTGATTTCAGACATTTTGCCCGAGTTCGTGA TCCATAATAACAACTATTCCGCCTCGGAAAAGGAAGAAAAAACCCAGGTGATTAAG CTGTTCAGTCGCTTCGCAACATCTTTCAAGGATTATTTCAAGAATCGCGCGAATTGCT TCAGTGCGGACGATATTTCTAGTTCAAGCTGCCATCGTATCGTTAATGATAACGCGG AGATTTTTTTTAGCAATGCTCTGGTGTACCGCCGCATTGTTAAGTCACTGTCCAACGA TGATATTAACAAGATCTCAGGAGACATGAAAGACTCGCTTAAAGAGATGAGTCTGG AAGAGATCTATTCTTATGAGAAGTATGGCGAGTTTATTACCCAAGAAGGAATCTCAT TCTACAATGATATTTGTGGAAAGGTGAACAGCTTTATGAATCTTTACTGCCAAAAAA ACAAGGAGAATAAGAATCTTTACAAACTTCAGAAGTTACATAAACAGATTTTGTGTA TTGCGGATACGTCTTATGAAGTCCCCTACAAATTTGAATCGGATGAAGAGGTATACC AAAGTGTGAACGGATTCTTGGACAATATTTCTTCTAAACATATTGTTGAACGCTTAC GTAAGATCGGGGATAACTACAATGGCTACAATCTTGACAAAATCTACATTGTTAGCA AATTCTACGAGAGTGTCAGCCAAAAGACGTACCGCGATTGGGAAACAATTAATACT GCGCTTGAGATTCACTATAATAACATTTTACCAGGCAACGGCAAGTCCAAGGCGGAT AAAGTTAAAAAAGCTGTTAAAAACGATTTGCAAAAATCTATCACAGAAATTAACGA GTTAGTTAGTAACTACAAACTGTGCTCCGATGACAACATTAAGGCTGAGACGTATAT CCATGAGATCTCTCACATCTTAAACAATTTTGAAGCTCAAGAACTTAAGTACAATCC GGAAATCCACCTGGTGGAATCCGAGCTGAAGGCTAGCGAACTGAAGAACGTATTGG ACGTGATCATGAACGCGTTCCACTGGTGTTCTGTCTTTATGACGGAAGAGCTTGTCG ACAAAGATAATAACTTTTACGCGGAACTTGAGGAAATTTACGATGAGATTTACCCAG TTATTTCATTGTATAACCTTGTCCGTAATTACGTGACCCAAAAGCCTTATAGTACGAA AAAAATCAAATTAAATTTTGGAATCCCAACACTGGCTGACGGTTGGAGCAAATCTA AGGAGTATTCTAATAACGCAATCATCTTAATGCGTGACAACCTGTATTATTTGGGTA TCTTCAATGCCAAAAATAAGCCTGACAAAAAGATTATCGAAGGAAATACTTCGGAG AATAAGGGGGATTACAAAAAAATGATTTACAATTTGCTGCCCGGGCCGAACAAGAT GATCCCCAAAGTGTTCTTATCCTCGAAGACTGGTGTAGAAACATACAAGCCAAGCGC ATACATTCTGGAGGGTTACAAGCAAAACAAACACATCAAATCTTCAAAAGACTTTG ACATTACATTTTGCCATGATCTTATTGACTACTTCAAAAACTGCATTGCTATTCACCC CGAGTGGAAGAACTTTGGGTTTGACTTCAGCGACACGTCTACGTATGAGGACATCTC CGGGTTCTACCGTGAAGTTGAGTTACAAGGGTATAAGATTGACTGGACGTATATTTC AGAGAAAGATATCGATCTTTTGCAGGAAAAGGGCCAGTTATATTTATTCCAGATTTA CAACAAGGACTTTAGTAAGAAGTCAACAGGAAATGACAACTTGCATACGATGTATT TGAAAAATCTTTTTTCTGAGGAAAATCTTAAGGACATCGTACTGAAATTGAATGGCG AGGCTGAAATCTTCTTCCGTAAATCCTCCATTAAGAATCCCATTATCCACAAAAAGG GGTCTATCCTGGTGAATCGTACCTACGAGGCAGAGGAGAAGGATCAATTCGGAAAT ATTCAGATTGTTCGTAAGAACATCCCCGAGAACATTTATCAAGAATTGTATAAGTAC TTTAATGACAAATCTGACAAAGAGTTATCCGACGAAGCTGCGAAACTGAAAAACGT TGTTGGTCACCACGAGGCCGCCACTAATATCGTAAAAGACTACCGTTATACCTATGA CAAGTACTTTTTGCACATGCCGATCACTATCAACTTCAAGGCGAATAAGACGGGCTT CATTAACGATCGTATCCTGCAATACATCGCCAAGGAGAAGGACCTTCACGTCATTGG GATTGACCGTGGTGAGCGTAACCTGATTTATGTAAGCGTCATTGATACCTGCGGTAA TATCGTCGAACAGAAAAGTTTCAACATTGTAAATGGATATGACTATCAGATCAAACT TAAGCAGCAGGAGGGTGCACGCCAGATTGCCCGCAAGGAATGGAAGGAGATTGGG AAGATTAAGGAAATTAAAGAAGGTTACTTATCACTGGTTATTCACGAGATCAGTAA AATGGTAATCAAATATAACGCGATCATTGCCATGGAGGATCTGAGCTATGGCTTTAA AAAGGGCCGTTTCAAAGTCGAGCGCCAGGTATATCAAAAGTTTGAAACAATGCTGA TTAACAAATTAAACTATCTGGTTTTCAAAGATATTTCGATCACTGAAAATGGCGGGC TGTTGAAGGGATACCAACTTACATACATCCCTGACAAACTGAAAAATGTCGGTCACC AATGTGGATGTATCTTTTATGTACCAGCAGCGTATACGAGCAAAATCGATCCAACTA CGGGTTTTGTGAACATCTTTAAGTTCAAGGATTTGACAGTAGATGCCAAACGCGAGT TCATTAAAAAATTTGATTCAATTCGCTACGATTCAGAGAAAAATCTTTTTTGTTTCAC GTTCGATTACAATAATTTCATTACGCAGAACACAGTAATGTCAAAGTCAAGCTGGTC GGTCTACACGTATGGAGTCCGTATTAAACGTCGTTTTGTAAACGGCCGTTTCTCAAA TGAATCAGATACAATTGATATTACGAAGGATATGGAGAAGACATTAGAGATGACTG ACATTAACTGGCGCGACGGACATGATCTTCGTCAGGACATTATTGATTATGAGATTG TACAGCATATCTTTGAGATCTTCCGCCTGACCGTTCAGATGCGCAATTCGTTGTCCGA GTTAGAAGACCGCGATTACGACCGTTTAATCAGTCCCGTCTTAAACGAAAATAACAT CTTCTACGATTCAGCCAAGGCAGGCGATGCCTTGCCAAAGGATGCTGACGCAAATG GCGCATACTGTATTGCGTTGAAAGGCCTTTATGAAATCAAGCAAATTACCGAAAACT GGAAAGAAGACGGAAAATTCTCCCGTGATAAGTTGAAAATCTCTAATAAGGATTGG TTCGATTTCATCCAAAATAAACGCTATTTGAAACGTCCGGCAGCGACCAAAAAAGCC GGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAAGA AACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 75 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAACGGAA CTAATAATTTCCAAAATTTTATAGGCATCTCTTCTTTACAGAAGACTCTTCGTAACGC CCTAATCCCGACTGAGACCACACAACAATTCATAGTGAAAAATGGGATCATTAAAG AAGACGAGCTGCGTGGGGAGAACAGGCAGATCCTAAAAGACATAATGGACGATTAT TATAGAGGGTTCATCTCAGAGACATTATCTAGCATCGACGACATTGACTGGACCTCC CTGTTTGAAAAAATGGAAATCCAGCTGAAGAATGGTGACAATAAAGACACATTAAT AAAAGAACAAACAGAGTACAGGAAAGCCATCCACAAGAAGTTCGCAAACGATGAC AGATTCAAAAATATGTTCAGTGCGAAGCTAATATCCGACATCTTACCAGAGTTTGTA ATACACAATAACAATTACAGCGCGAGCGAAAAGGAAGAGAAAACGCAAGTAATTA AGCTTTTTAGTAGGTTCGCTACCTCTTTCAAAGATTACTTCAAAAATCGTGCTAACTG CTTCTCAGCCGACGACATATCTTCAAGTTCCTGTCACCGTATCGTGAATGATAACGC TGAGATATTCTTCTCAAACGCCCTTGTATACCGTAGGATCGTAAAGTCCTTATCTAAC GATGATATAAACAAGATCAGTGGAGACATGAAAGACAGCCTTAAAGAGATGTCTCT AGAAGAAATTTACTCCTATGAAAAGTATGGGGAGTTTATAACACAGGAGGGGATCA GCTTCTACAACGACATCTGCGGAAAGGTGAACAGTTTCATGAATCTTTACTGCCAGA AGAATAAAGAGAACAAAAATCTTTATAAGCTTCAAAAGTTGCACAAACAAATACTG TGCATTGCCGATACATCATATGAGGTCCCCTATAAGTTCGAATCTGATGAGGAAGTT TATCAATCTGTTAACGGCTTTCTAGACAATATCAGCTCAAAACACATCGTAGAAAGA CTGAGGAAAATAGGTGATAATTATAATGGATACAACTTGGATAAAATATATATAGT CTCTAAATTTTACGAGTCAGTATCCCAGAAAACGTATAGGGATTGGGAGACCATCAA CACGGCGTTAGAGATTCATTACAATAACATCTTACCGGGAAACGGAAAAAGTAAGG CGGACAAAGTAAAGAAAGCCGTTAAAAATGACTTACAAAAGAGTATAACAGAAAT AAACGAACTAGTAAGCAACTACAAGCTTTGTTCCGATGATAATATCAAGGCCGAGA CATATATCCATGAGATCTCCCACATTCTAAACAATTTCGAAGCGCAAGAACTTAAAT ATAATCCCGAAATCCACCTGGTGGAAAGTGAACTAAAGGCTAGTGAGTTAAAGAAC GTTCTTGATGTTATCATGAACGCCTTCCATTGGTGCTCTGTTTTTATGACCGAGGAGT TGGTTGATAAAGATAATAATTTCTACGCTGAATTAGAGGAGATATACGACGAAATCT ACCCAGTGATTTCACTATACAACTTGGTCAGGAACTATGTTACACAAAAGCCGTACA GCACTAAGAAAATTAAGCTAAATTTCGGTATCCCCACGTTAGCCGACGGGTGGAGC AAGTCCAAAGAATATTCCAACAATGCGATTATTTTAATGCGTGACAATCTTTATTAC CTTGGCATCTTCAATGCCAAAAACAAACCTGACAAAAAGATTATAGAAGGTAATAC GTCCGAGAACAAAGGCGATTACAAGAAGATGATTTATAACCTACTGCCCGGACCAA ACAAAATGATCCCCAAAGTTTTTCTTAGTTCTAAAACCGGCGTAGAGACGTATAAAC CTTCTGCCTATATCTTAGAGGGATATAAGCAGAACAAACATATCAAATCTTCCAAGG ACTTTGATATTACATTCTGCCACGATTTAATTGACTACTTCAAAAATTGCATAGCGAT ACATCCGGAGTGGAAGAACTTTGGCTTCGACTTCAGTGATACATCCACCTATGAGGA TATATCAGGCTTCTATCGTGAGGTCGAATTGCAAGGGTACAAAATCGATTGGACGTA TATATCCGAGAAAGACATAGACCTTCTTCAAGAAAAGGGGCAGTTATATTTATTCCA AATATACAACAAGGACTTCAGTAAGAAGTCAACAGGTAATGACAACTTACACACCA TGTACTTGAAAAATTTATTTTCTGAAGAAAACCTAAAGGACATTGTACTAAAACTGA ACGGGGAGGCAGAAATTTTTTTTAGAAAGAGCAGCATAAAAAACCCAATAATTCAT AAGAAAGGAAGCATTTTAGTTAATAGGACGTACGAGGCAGAGGAAAAGGACCAGTT TGGCAATATCCAGATCGTAAGGAAAAATATTCCTGAAAACATATATCAGGAACTAT ATAAATACTTTAACGACAAATCCGACAAAGAATTATCCGACGAGGCTGCAAAGCTG AAGAACGTCGTAGGGCACCATGAGGCAGCGACTAATATTGTGAAAGACTATAGGTA TACATACGACAAATACTTTCTGCACATGCCCATCACGATTAACTTCAAGGCGAACAA GACGGGATTCATTAACGACCGTATATTACAATATATTGCTAAGGAGAAAGATCTGCA TGTAATAGGTATCGACAGAGGCGAACGTAATTTAATCTACGTGTCCGTCATCGACAC GTGCGGGAACATCGTAGAGCAAAAGAGTTTTAATATAGTAAATGGCTATGATTACC AAATTAAGCTAAAGCAGCAAGAAGGAGCAAGACAGATAGCTAGGAAAGAATGGAA GGAGATAGGAAAAATAAAGGAGATCAAGGAGGGGTATCTTAGCCTAGTAATTCATG AAATATCTAAGATGGTTATCAAATACAACGCTATCATAGCGATGGAAGACTTATCTT ATGGTTTCAAGAAAGGAAGGTTCAAAGTAGAGCGTCAAGTTTATCAAAAGTTCGAA ACGATGTTGATTAATAAACTAAACTATTTGGTATTTAAAGATATATCTATCACCGAG AATGGTGGTCTACTAAAGGGTTACCAGCTTACATACATACCGGACAAACTTAAAAA CGTCGGACATCAGTGTGGATGCATTTTCTACGTTCCAGCTGCATATACCAGCAAGAT CGACCCAACGACTGGGTTCGTAAATATTTTTAAATTCAAGGATTTGACTGTCGACGC CAAAAGAGAGTTCATAAAAAAGTTCGATTCAATTAGGTACGACAGCGAAAAGAATT TGTTCTGCTTTACTTTTGACTATAACAATTTCATTACTCAGAACACTGTAATGTCTAA GTCCTCTTGGTCAGTCTATACTTATGGCGTTCGTATCAAACGTAGATTTGTTAACGGT AGATTCTCAAATGAAAGTGATACAATAGATATCACGAAAGATATGGAGAAAACATT AGAAATGACAGACATAAACTGGAGAGACGGACATGACTTGAGACAGGACATTATTG ACTACGAGATCGTGCAGCACATCTTTGAGATCTTTCGTTTGACCGTACAAATGCGTA ACAGTTTATCTGAGCTTGAGGACAGGGACTACGATAGATTGATATCACCTGTATTAA ATGAGAATAACATCTTCTATGATTCCGCAAAAGCAGGCGACGCTCTACCCAAAGAC GCTGATGCGAACGGTGCTTATTGCATAGCTTTAAAGGGTTTGTATGAGATCAAACAG ATAACAGAAAATTGGAAGGAAGATGGTAAGTTCTCCCGTGACAAGCTTAAAATATC AAATAAGGACTGGTTCGATTTTATACAGAATAAGCGTTATTAAAACGTCCGGCAGCG ACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCA GCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCG GGCTAA SEQ ID NO: 76 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAATGGAA CTAATAACTTCCAGAATTTCATTGGTATCTCCTCTTTACAAAAAACTCTAAGAAACG CCCTAATTCCGACTGAAACTACACAGCAATTCATCGTCAAAAACGGGATCATTAAGG AGGATGAGTTGAGGGGTGAAAATCGTCAAATTCTTAAAGACATCATGGACGACTAC TACAGGGGGTTCATCAGCGAGACGTTATCTAGTATAGACGATATAGACTGGACTTCA CTGTTCGAGAAGATGGAAATCCAATTAAAAAATGGGGACAATAAAGATACACTTAT AAAGGAACAGACAGAGTATAGAAAGGCAATACACAAAAAGTTTGCCAACGACGAT CGTTTCAAGAACATGTTTAGTGCTAAATTGATTTCAGATATTCTGCCGGAATTTGTTA TTCACAACAATAATTATAGCGCCAGTGAGAAAGAAGAAAAAACGCAGGTTATCAAA CTGTTCAGTCGTTTCGCTACATCTTTTAAGGATTACTTTAAAAACCGTGCAAATTGTT TTTCAGCCGACGATATTAGTAGCAGCTCTTGTCACCGTATTGTTAATGATAATGCGG AGATTTTCTTTTCAAACGCATTGGTCTACAGGAGGATAGTCAAGTCCCTTTCAAATG ACGACATTAATAAGATCTCAGGTGACATGAAAGATTCCTTAAAGGAAATGTCCCTG GAAGAGATCTATTCCTATGAAAAGTACGGTGAGTTCATTACTCAAGAGGGTATAAG CTTTTACAATGACATATGTGGTAAGGTTAATAGCTTTATGAACCTGTATTGCCAGAA GAACAAAGAAAATAAGAATCTGTATAAGTTGCAAAAGCTACACAAACAAATTTTGT GCATTGCCGATACATCATACGAGGTGCCATACAAATTCGAGAGCGATGAGGAGGTT TATCAGAGCGTGAATGGATTCCTGGACAATATTAGTAGTAAGCATATCGTGGAAAG GCTTAGAAAGATAGGTGACAATTACAATGGCTACAATCTGGATAAAATCTACATCGT CTCAAAATTCTATGAAAGTGTATCCCAGAAGACGTACCGTGATTGGGAAACTATCAA CACCGCTCTGGAGATACATTACAACAATATACTTCCCGGAAACGGCAAGTCAAAAG CCGACAAAGTCAAAAAAGCGGTCAAGAACGATTTACAAAAGTCTATCACTGAAATT AATGAATTAGTTAGTAATTACAAACTGTGTAGTGATGATAATATTAAGGCAGAGACT TACATACACGAAATTTCACACATTTTAAACAACTTCGAGGCACAGGAACTTAAATAT AATCCTGAAATTCACCTGGTTGAAAGTGAATTGAAAGCCAGCGAGCTAAAGAACGT TTTGGACGTAATCATGAACGCATTCCACTGGTGCTCTGTCTTTATGACAGAGGAACT AGTGGATAAGGACAATAATTTTTATGCGGAGCTGGAGGAAATATACGATGAGATAT ATCCCGTAATATCATTATATAATCTGGTAAGAAACTATGTGACTCAAAAGCCGTATA GCACCAAGAAAATTAAACTTAATTTCGGCATACCCACTTTAGCGGACGGCTGGTCAA AATCCAAAGAGTATAGTAATAATGCCATCATCCTGATGCGTGACAACCTGTACTATT TAGGTATATTTAACGCCAAAAATAAACCCGACAAAAAGATTATAGAGGGCAACACC TCAGAGAACAAAGGTGATTATAAGAAGATGATTTACAACCTTTTACCCGGTCCTAAT AAGATGATTCCCAAAGTCTTTCTATCTAGCAAAACTGGTGTTGAAACATACAAACCC TCAGCTTATATTTTAGAAGGGTATAAGCAGAATAAGCATATTAAAAGCTCCAAAGAT TTCGATATTACCTTTTGCCATGACTTGATAGACTATTTCAAAAATTGTATTGCCATTC ACCCTGAATGGAAAAACTTCGGATTTGACTTCTCTGACACATCCACCTACGAAGACA TTTCAGGTTTTTACAGGGAAGTCGAGCTACAGGGTTATAAAATTGATTGGACATACA TCAGCGAGAAAGATATTGACCTACTTCAAGAAAAAGGGCAGCTATACCTGTTCCAG ATATACAATAAAGACTTCAGTAAAAAAAGCACCGGGAACGATAATCTTCACACAAT GTACTTAAAAAATTTATTTAGTGAAGAGAATCTGAAGGATATAGTGCTGAAGTTAAA CGGGGAGGCAGAGATATTTTTTAGAAAATCTAGTATTAAGAATCCGATCATCCACAA GAAGGGTTCTATCCTTGTTAATAGGACTTATGAGGCAGAAGAAAAAGACCAATTCG GCAACATACAAATTGTCCGTAAAAATATCCCTGAGAACATTTATCAGGAACTATACA AGTACTTCAATGATAAAAGCGACAAGGAGCTGAGCGACGAGGCTGCTAAGTTAAAG AATGTGGTGGGCCACCATGAGGCAGCAACGAATATTGTGAAGGACTATCGTTATAC CTACGATAAATACTTTCTTCATATGCCGATCACCATTAATTTCAAGGCAAACAAAAC TGGCTTCATTAACGATCGTATCTTACAATATATCGCAAAAGAGAAAGACCTTCACGT TATCGGGATCGATAGAGGCGAGCGTAACCTAATTTATGTTTCTGTGATAGACACCTG TGGGAACATAGTCGAACAGAAATCATTTAATATTGTTAACGGCTACGATTATCAGAT AAAGTTGAAGCAACAAGAGGGTGCACGTCAAATAGCAAGGAAAGAATGGAAAGAA ATAGGCAAGATTAAAGAAATAAAAGAAGGTTATTTATCCCTTGTAATACACGAAAT TAGCAAAATGGTGATTAAATATAATGCGATCATTGCCATGGAGGATCTTTCTTACGG CTTCAAAAAGGGGAGATTCAAAGTCGAGAGGCAGGTGTATCAGAAGTTTGAGACCA TGCTAATCAATAAACTAAATTATCTAGTATTCAAAGACATAAGCATCACCGAAAATG GCGGCTTGTTGAAGGGTTATCAATTGACCTACATCCCAGATAAACTAAAAAACGTAG GGCATCAATGCGGATGTATATTTTACGTTCCAGCCGCATACACTTCCAAAATCGATC CAACTACGGGTTTTGTGAACATCTTCAAATTCAAAGACTTGACTGTCGATGCTAAGA GGGAGTTTATCAAGAAATTTGACTCCATTAGATACGACAGTGAGAAGAATCTGTTCT GTTTTACCTTTGATTATAACAACTTTATAACTCAAAACACAGTCATGAGTAAGTCAT CTTGGTCAGTGTATACGTATGGTGTGAGGATTAAAAGGAGGTTTGTTAACGGGAGAT TTTCCAATGAAAGTGATACAATAGATATAACCAAGGACATGGAAAAGACTCTTGAA ATGACCGACATTAACTGGAGAGATGGCCACGACTTACGTCAAGATATAATCGATTA CGAGATAGTGCAACATATCTTTGAGATATTTAGGCTTACTGTCCAAATGCGTAACTC ATTAAGTGAGTTGGAGGACAGGGATTACGATAGGCTAATAAGTCCTGTTCTTAACGA AAACAATATATTCTACGATTCAGCAAAGGCGGGAGACGCCCTGCCCAAGGACGCGG ATGCTAACGGCGCATACTGTATTGCCCTGAAAGGCTTGTACGAGATAAAACAGATC ACGGAGAACTGGAAAGAAGATGGAAAATTCAGTCGTGACAAGTTAAAAATTAGTAA CAAAGACTGGTTCGACTTTATTCAGAACAAGAGATATCTGAAACGTCCGGCAGCGA CCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAG CCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGG GCTAA SEQ ID NO: 77 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAACGGAA CCAATAACTTTCAAAACTTTATAGGCATCTCCAGTCTACAGAAGACACTACGTAACG CTTTGATACCAACTGAGACCACGCAGCAGTTTATCGTCAAGAACGGTATTATAAAGG AAGACGAGCTAAGGGGGGAAAACCGTCAGATCTTAAAGGACATCATGGATGACTAC TACAGAGGCTTCATAAGTGAGACTTTGTCTAGTATAGACGACATCGACTGGACCAGT TTATTTGAGAAGATGGAAATTCAGTTAAAGAACGGGGACAATAAAGACACACTAAT TAAAGAGCAGACCGAATACAGAAAAGCTATACACAAAAAGTTTGCCAACGATGATA GATTCAAAAATATGTTTTCAGCAAAATTGATTTCCGACATATTGCCAGAATTCGTAA TCCATAATAACAATTATTCTGCAAGTGAGAAGGAAGAGAAGACCCAAGTAATCAAG CTGTTTTCCCGTTTTGCTACGAGTTTCAAAGATTATTTCAAGAATAGGGCTAATTGTT TCTCCGCGGACGACATAAGTAGCAGTTCCTGTCACAGGATTGTGAACGATAATGCTG AGATATTTTTTTCCAATGCCCTAGTGTATAGGAGAATAGTTAAAAGCTTAAGCAACG ACGATATCAATAAAATTTCAGGGGACATGAAGGACAGCTTAAAGGAAATGAGTTTG GAGGAGATTTACAGTTATGAAAAATACGGAGAGTTTATAACTCAGGAAGGCATCTC TTTCTATAATGATATCTGTGGGAAGGTAAACTCCTTCATGAATTTATATTGCCAGAA GAATAAGGAAAACAAAAATCTTTACAAGCTTCAAAAGTTACATAAGCAGATCTTAT GTATTGCCGACACGAGTTATGAAGTGCCTTATAAATTCGAGAGTGATGAGGAAGTGT ATCAGTCTGTTAACGGATTCCTAGATAATATAAGTTCCAAACATATAGTCGAGAGGC TGAGGAAGATTGGCGATAACTATAATGGATATAATCTTGACAAAATCTATATAGTCT CTAAATTTTATGAAAGCGTCAGCCAGAAGACATATAGAGATTGGGAAACTATAAAC ACAGCCCTTGAAATACATTACAATAACATCCTACCCGGCAATGGTAAGTCTAAGGCA GACAAAGTTAAAAAAGCAGTAAAGAATGACTTACAGAAGTCAATCACGGAGATAA ATGAGTTGGTCAGTAACTACAAATTATGCTCCGACGATAATATTAAGGCCGAAACAT ATATACACGAGATAAGTCATATATTAAACAATTTCGAAGCCCAGGAGTTAAAATAT AACCCTGAAATTCATCTGGTCGAAAGTGAGTTAAAGGCCAGTGAGTTAAAGAATGT ACTTGACGTAATTATGAATGCTTTTCATTGGTGCTCCGTGTTCATGACCGAGGAGTTA GTAGATAAAGACAATAACTTTTACGCCGAACTTGAAGAGATATACGACGAGATTTA TCCGGTAATCAGCTTGTACAACTTAGTTAGAAATTATGTAACACAGAAGCCTTACTC TACTAAAAAAATAAAACTGAACTTTGGTATCCCAACTCTTGCAGATGGTTGGAGTAA AAGCAAGGAATATAGCAACAATGCGATCATCTTGATGAGAGACAACTTGTACTATTT GGGAATCTTCAACGCGAAAAATAAACCCGACAAAAAAATCATCGAAGGGAATACCT CTGAGAATAAAGGTGACTATAAGAAAATGATTTACAATCTACTTCCTGGTCCTAATA AAATGATCCCGAAAGTGTTTCTTAGTTCTAAGACTGGTGTCGAGACGTACAAACCTA GCGCGTACATCTTAGAAGGGTACAAGCAGAATAAACACATCAAATCAAGCAAAGAC TTCGATATTACTTTTTGCCATGACTTGATAGACTACTTTAAAAACTGCATAGCAATCC ACCCGGAGTGGAAAAACTTTGGCTTTGATTTCTCTGACACCTCTACATATGAGGACA TATCTGGTTTTTACCGTGAGGTTGAATTGCAGGGATACAAAATTGACTGGACTTACA TATCTGAAAAAGATATCGATCTATTGCAGGAGAAAGGCCAGCTTTACCTTTTCCAGA TCTATAATAAGGACTTCTCTAAGAAGTCTACAGGGAATGATAATTTGCACACTATGT ACTTAAAAAATCTGTTTTCCGAGGAAAACTTGAAAGACATTGTTTTAAAGTTGAACG GAGAAGCTGAAATATTTTTCAGAAAGAGCTCCATAAAAAACCCGATCATTCATAAG AAGGGATCTATCCTGGTTAACAGAACGTACGAAGCGGAAGAAAAAGACCAATTCGG AAACATTCAAATTGTTAGAAAGAATATCCCTGAGAACATCTACCAGGAGTTATATAA GTATTTTAATGATAAGTCAGATAAGGAACTATCTGACGAAGCGGCGAAGCTTAAAA ATGTTGTAGGACACCATGAGGCTGCTACAAATATAGTCAAGGACTACCGTTATACCT ACGATAAGTACTTTCTACACATGCCCATTACCATCAATTTTAAAGCTAATAAAACGG GTTTTATCAACGATCGTATCCTACAATATATTGCGAAAGAGAAGGATTTGCATGTCA TTGGCATTGATAGAGGTGAGAGGAACCTAATATACGTATCCGTGATTGATACGTGCG GGAACATAGTTGAACAGAAATCATTTAATATAGTTAATGGGTACGACTATCAGATTA AGCTAAAGCAACAAGAAGGCGCCAGGCAAATTGCCCGTAAAGAATGGAAAGAGAT CGGGAAGATCAAGGAAATAAAAGAAGGATACCTTTCCCTGGTCATCCATGAAATTA GCAAAATGGTGATTAAGTACAATGCCATAATCGCGATGGAGGACTTAAGCTACGGG TTCAAAAAGGGGAGGTTTAAGGTGGAGAGGCAAGTGTACCAGAAATTTGAGACCAT GCTAATCAACAAACTGAACTACCTAGTTTTTAAGGACATTTCAATTACAGAGAATGG AGGACTTTTAAAGGGTTACCAACTAACGTATATACCAGATAAGTTGAAAAATGTCG GTCACCAGTGTGGCTGCATCTTTTACGTTCCCGCCGCTTATACATCTAAAATTGATCC AACCACAGGCTTTGTAAATATCTTTAAATTCAAAGATTTAACTGTGGATGCAAAAAG AGAGTTTATCAAGAAATTCGATAGCATTCGTTATGATAGCGAGAAGAACCTGTTCTG CTTTACTTTCGACTATAACAACTTTATAACTCAAAACACCGTGATGTCAAAAAGCTC ATGGTCAGTCTACACCTATGGTGTAAGGATTAAAAGGCGTTTCGTGAATGGGAGATT CTCCAATGAAAGTGACACGATCGACATAACAAAGGACATGGAGAAGACACTAGAG ATGACTGATATTAATTGGAGAGACGGACACGATCTGCGTCAAGATATAATTGATTAT GAGATAGTACAGCACATATTTGAGATCTTCCGTTTGACTGTCCAAATGCGTAATTCC CTTTCTGAGCTGGAAGATAGGGACTATGATAGATTAATATCCCCTGTACTAAATGAG AACAACATTTTCTATGATAGTGCAAAAGCCGGGGATGCATTGCCGAAAGACGCTGA CGCTAATGGGGCGTACTGTATAGCTTTAAAGGGGCTTTACGAAATAAAGCAGATAA CCGAAAACTGGAAGGAAGATGGCAAATTCTCAAGGGACAAACTTAAGATCTCTAAC AAGGATTGGTTCGATTTTATACAAAACAAACGTTATTTGAAACGTCCGGCAGCGACC AAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCC CGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGG CTAA SEQ ID NO: 78 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAATAATGGTA CAAACAACTTTCAGAATTTCATTGGGATCTCTAGCTTACAGAAGACCCTGAGGAATG CGTTGATTCCAACTGAAACAACCCAGCAATTCATCGTGAAAAATGGGATAATCAAA GAGGATGAGTTAAGGGGTGAAAACCGTCAAATATTGAAGGATATTATGGACGACTA CTACCGTGGATTCATCTCAGAGACGTTGAGCAGCATTGACGACATAGACTGGACTAG CCTTTTCGAGAAGATGGAAATTCAGTTAAAGAACGGAGATAACAAAGATACACTAA TCAAGGAACAGACAGAATACAGAAAAGCAATTCATAAGAAATTCGCTAATGACGAT CGTTTTAAAAACATGTTCTCTGCAAAATTAATTAGCGACATTCTGCCGGAATTCGTT ATACATAATAATAACTACAGTGCTTCTGAAAAGGAAGAGAAAACTCAGGTAATAAA ACTGTTCTCTCGTTTTGCCACATCCTTCAAAGACTACTTTAAAAATAGAGCGAACTG CTTTAGCGCCGACGATATTAGTTCTTCCTCATGCCACAGGATTGTCAACGATAATGC AGAGATATTCTTTTCTAACGCACTAGTCTACAGAAGGATTGTAAAGTCTTTGTCAAA TGATGACATAAACAAGATTAGTGGAGATATGAAAGACTCTCTAAAGGAAATGAGCC TTGAGGAGATATACTCTTATGAAAAGTACGGTGAGTTTATTACCCAAGAAGGCATTA GTTTCTATAATGACATTTGTGGAAAAGTTAACAGTTTTATGAATCTATACTGTCAAA AAAATAAGGAGAATAAAAATCTTTATAAGTTGCAAAAACTGCATAAGCAGATATTA TGTATAGCAGACACGAGCTATGAGGTACCGTACAAGTTCGAGAGCGATGAGGAAGT CTACCAATCTGTCAACGGATTTTTGGACAACATTTCTTCAAAACATATTGTGGAGAG GCTTAGGAAAATAGGCGACAATTATAATGGATATAACTTAGATAAGATATATATTGT TTCCAAATTCTACGAATCTGTAAGCCAGAAGACATACAGAGATTGGGAAACGATAA ACACAGCCCTTGAAATTCACTATAACAACATACTACCTGGAAACGGCAAATCAAAG GCCGACAAAGTTAAGAAGGCCGTAAAGAATGATTTACAGAAGAGCATAACGGAGAT CAATGAGCTGGTGTCTAACTATAAATTGTGTAGCGATGACAACATAAAAGCCGAGA CTTACATTCACGAAATTTCACACATACTTAACAACTTTGAAGCTCAGGAATTAAAGT ATAATCCCGAAATACACCTTGTGGAGTCCGAACTAAAGGCTAGTGAGCTTAAGAAC GTCCTAGACGTAATTATGAATGCCTTCCACTGGTGTAGTGTTTTTATGACCGAGGAA CTTGTTGACAAAGATAATAATTTTTATGCAGAACTAGAAGAGATATACGATGAAATA TACCCGGTGATCAGTTTGTACAATCTTGTCAGGAACTATGTGACACAAAAGCCCTAT TCAACAAAGAAAATAAAACTTAATTTCGGAATTCCTACGTTAGCTGATGGCTGGTCT AAATCCAAGGAATACAGCAACAACGCTATAATTCTGATGAGAGATAACTTGTACTA TCTAGGCATCTTCAATGCCAAAAATAAGCCTGATAAGAAGATTATAGAGGGCAACA CTTCAGAGAACAAGGGCGACTACAAGAAAATGATCTATAACCTATTGCCTGGCCCA AACAAGATGATTCCGAAGGTCTTCCTATCATCCAAGACCGGCGTTGAGACATACAA GCCATCAGCGTATATTTTAGAGGGGTACAAACAAAACAAGCACATAAAGTCTAGTA AAGACTTCGATATAACATTTTGTCATGACTTAATTGACTACTTTAAGAATTGCATCGC TATACACCCGGAATGGAAGAATTTCGGCTTCGACTTCTCTGATACATCTACCTACGA GGACATTAGCGGGTTTTACCGTGAAGTCGAATTACAAGGGTATAAGATAGATTGGA CGTACATCTCTGAGAAAGACATAGACTTGCTTCAGGAAAAGGGCCAGTTGTATCTAT TCCAAATATACAATAAGGATTTTTCCAAGAAATCTACGGGTAATGACAATCTTCACA CAATGTATCTTAAGAACCTTTTCTCAGAAGAGAACCTGAAGGACATTGTCTTAAAAC TAAATGGCGAAGCTGAGATTTTTTTCAGGAAGTCTTCAATTAAGAACCCGATAATCC ACAAGAAGGGGAGTATTCTTGTGAATAGAACTTACGAGGCCGAAGAAAAAGACCAA TTTGGTAACATCCAGATAGTCAGAAAGAACATTCCAGAGAACATCTACCAAGAGCT ATACAAATATTTCAACGACAAGTCCGATAAGGAACTGTCCGATGAGGCAGCCAAGT TGAAGAATGTCGTGGGTCATCATGAAGCTGCTACTAACATTGTCAAGGACTATCGTT ATACTTACGACAAGTATTTCCTACACATGCCGATAACAATTAATTTCAAGGCTAACA AAACAGGCTTTATCAACGATCGTATCTTGCAGTACATAGCTAAGGAAAAGGATTTGC ATGTGATTGGCATTGATAGAGGGGAGCGTAACTTGATATATGTGTCTGTCATAGACA CGTGTGGCAACATCGTCGAACAGAAATCATTCAACATAGTAAACGGCTACGATTAC CAAATTAAGCTGAAACAGCAAGAGGGTGCACGTCAAATTGCGCGTAAAGAGTGGAA AGAAATTGGTAAAATCAAGGAAATTAAAGAAGGCTACTTGTCTCTTGTTATACATGA AATTTCCAAGATGGTTATAAAGTATAACGCGATAATTGCTATGGAAGACTTATCATA CGGGTTTAAAAAGGGGAGGTTCAAGGTAGAGAGGCAGGTCTATCAAAAGTTCGAGA CGATGTTGATTAATAAACTAAACTATCTAGTGTTCAAAGATATCAGCATTACGGAGA ACGGGGGGCTACTGAAAGGATATCAACTAACGTACATTCCCGATAAGTTAAAGAAC GTTGGTCATCAATGTGGTTGCATCTTCTACGTGCCTGCTGCCTATACGTCCAAAATAG ATCCAACTACTGGATTTGTTAACATCTTTAAATTCAAAGATTTAACCGTAGACGCCA AAAGGGAATTTATAAAAAAATTTGACAGCATCCGTTACGATAGCGAAAAGAATCTG TTCTGTTTTACTTTCGACTACAATAATTTCATCACGCAAAATACGGTAATGTCTAAGT CAAGTTGGAGCGTCTACACGTATGGAGTCAGGATCAAGAGGCGTTTCGTAAATGGA AGATTCTCTAATGAGTCAGATACTATAGACATCACGAAAGATATGGAGAAAACCTT GGAGATGACGGATATTAACTGGCGTGATGGACACGATTTAAGACAGGACATTATTG ACTATGAGATTGTGCAACACATCTTCGAAATATTCCGTCTAACAGTCCAAATGAGGA ATAGCCTAAGTGAATTGGAGGACCGTGATTACGATAGGCTTATAAGTCCTGTCCTTA ACGAAAACAATATTTTCTATGATAGTGCTAAGGCGGGGGACGCACTGCCTAAAGAC GCAGATGCTAACGGGGCATACTGCATTGCGTTAAAGGGTCTGTACGAAATCAAGCA GATTACGGAAAACTGGAAAGAGGATGGCAAGTTTAGCAGAGATAAGTTGAAGATAA GTAACAAAGATTGGTTTGACTTTATTCAGAATAAAAGGTATTTAAAACGTCCGGCAG CGACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGG CAGCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTC CGGGCTAA SEQ ID NO: 79 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAATAACGGCA CTAATAATTTCCAGAATTTCATCGGCATTAGCAGCTTACAAAAGACGTTGAGGAATG CCTTAATACCCACAGAAACTACTCAACAATTTATAGTGAAGAATGGGATAATTAAG GAAGACGAGTTGAGAGGTGAAAATAGGCAAATCTTGAAAGACATTATGGATGACTA CTACAGGGGCTTCATTAGTGAAACGTTGTCTTCAATAGATGACATTGATTGGACTTC TTTGTTTGAGAAGATGGAAATACAGTTAAAGAACGGCGACAATAAGGATACACTTA TCAAAGAGCAAACAGAATATAGAAAAGCAATTCACAAAAAGTTTGCTAACGATGAT AGGTTCAAGAACATGTTTAGCGCTAAACTAATATCAGACATCCTTCCCGAGTTCGTT ATTCATAACAATAACTATAGTGCAAGTGAAAAAGAGGAGAAGACACAGGTGATTAA GCTGTTCTCCAGATTCGCGACTTCTTTCAAAGATTACTTCAAAAACAGAGCCAACTG TTTTTCAGCTGACGATATCTCTAGTAGTAGTTGTCACCGTATAGTGAACGATAACGC TGAGATCTTCTTTAGCAATGCATTAGTGTATAGAAGGATAGTTAAGTCTCTAAGCAA TGATGATATCAATAAAATTTCCGGAGACATGAAGGACTCCCTAAAGGAAATGTCCTT AGAAGAGATCTACTCATATGAGAAATACGGGGAATTTATTACGCAGGAAGGGATCT CCTTTTACAATGACATATGCGGGAAGGTCAACTCTTTCATGAACTTATACTGCCAAA AGAACAAGGAGAACAAGAATTTATATAAACTTCAGAAACTTCACAAACAAATACTG TGCATAGCCGATACCTCATATGAGGTTCCTTACAAATTTGAATCAGATGAAGAGGTA TACCAATCCGTTAACGGCTTTCTTGACAATATTAGCTCAAAGCACATCGTGGAGAGG TTGAGAAAGATTGGTGATAATTATAATGGCTACAATCTAGATAAGATATATATTGTT AGCAAGTTCTACGAGTCTGTGTCCCAAAAAACATATAGGGATTGGGAGACAATTAA TACTGCTCTAGAAATCCATTACAACAACATCCTTCCTGGAAATGGCAAGAGTAAGGC CGACAAAGTCAAGAAAGCAGTGAAAAATGATCTGCAAAAATCAATTACTGAGATAA ACGAGCTAGTATCTAATTACAAGCTTTGTAGCGACGATAACATTAAGGCAGAAACG TACATACACGAGATTAGTCACATCTTAAATAATTTTGAAGCCCAAGAACTGAAATAT AACCCTGAGATACACCTTGTTGAATCCGAGTTAAAGGCGTCTGAACTAAAAAACGT GTTAGACGTTATTATGAATGCCTTCCACTGGTGTAGCGTCTTTATGACTGAGGAGTT GGTTGATAAGGATAATAACTTTTACGCTGAATTGGAAGAAATTTATGACGAAATCTA TCCTGTTATTTCTCTATATAATTTGGTGAGAAATTACGTAACGCAAAAGCCCTATAGT ACGAAAAAAATAAAACTAAATTTCGGGATCCCTACCCTAGCCGACGGTTGGTCTAA ATCCAAGGAGTACTCAAACAATGCAATAATATTGATGAGGGACAACCTGTACTACC TAGGCATATTTAATGCCAAAAATAAGCCCGATAAAAAGATTATAGAAGGGAACACG TCAGAAAATAAAGGAGACTATAAGAAAATGATCTACAACCTTTTGCCCGGCCCCAA TAAAATGATCCCGAAGGTCTTCCTAAGTAGCAAGACTGGCGTAGAGACCTACAAAC CATCTGCATACATTTTGGAGGGGTACAAGCAAAACAAGCACATAAAGAGTAGTAAG GATTTTGACATTACATTCTGCCATGACTTAATTGACTACTTTAAAAATTGCATCGCAA TTCACCCTGAATGGAAAAATTTTGGATTTGATTTCTCTGATACTTCAACATATGAGG ATATTTCAGGGTTCTACAGGGAGGTCGAACTACAGGGTTACAAAATAGACTGGACG TATATTTCTGAGAAAGATATAGATTTGCTTCAGGAAAAGGGTCAGCTATATCTGTTC CAGATATATAATAAGGACTTCTCCAAAAAGAGTACCGGAAATGATAATCTGCACAC AATGTACTTAAAAAACTTGTTCTCTGAGGAGAATCTAAAAGACATCGTACTAAAACT TAACGGGGAGGCCGAAATTTTTTTTAGGAAGTCCAGCATCAAGAACCCGATTATTCA TAAAAAAGGTAGCATTTTGGTGAACCGTACTTATGAGGCGGAAGAAAAAGACCAAT TCGGTAATATTCAAATCGTTAGAAAGAACATCCCTGAGAACATTTATCAGGAACTAT ACAAATACTTTAACGACAAATCAGATAAGGAGCTTTCTGATGAGGCAGCTAAATTG AAAAATGTAGTGGGACATCACGAAGCAGCCACTAACATAGTGAAGGACTACAGATA CACATACGATAAGTACTTCCTGCACATGCCTATTACAATTAACTTTAAAGCAAATAA AACAGGGTTTATTAACGACAGAATCTTACAGTATATTGCCAAAGAAAAGGATCTGC ATGTGATAGGAATAGACAGAGGAGAAAGAAACCTGATATACGTCTCCGTGATTGAT ACATGTGGGAACATAGTAGAACAGAAGTCCTTTAACATTGTTAATGGGTACGATTAT CAAATTAAATTAAAACAACAAGAAGGAGCACGTCAAATAGCTAGGAAAGAATGGA AAGAGATAGGAAAAATTAAGGAAATTAAGGAGGGTTACCTGTCCCTTGTAATTCAT GAAATATCCAAAATGGTAATTAAATATAACGCGATCATCGCGATGGAAGATCTAAG CTACGGGTTCAAAAAAGGCAGGTTTAAGGTGGAGAGGCAAGTTTACCAAAAGTTCG AGACAATGTTGATTAATAAGTTAAACTACTTAGTTTTCAAAGATATCTCCATAACCG AGAATGGCGGGCTTTTAAAAGGGTACCAACTAACATATATCCCGGATAAATTGAAG AACGTTGGACACCAGTGTGGCTGCATATTTTATGTACCCGCTGCGTATACTTCTAAA ATTGACCCGACCACCGGGTTTGTAAACATATTCAAGTTTAAGGACCTAACAGTTGAC GCCAAACGTGAGTTCATCAAGAAGTTCGATAGTATAAGGTATGACTCTGAGAAGAA CCTTTTCTGCTTCACGTTTGACTATAATAATTTCATCACCCAAAATACAGTTATGTCA AAAAGCTCTTGGTCAGTATATACGTATGGCGTAAGGATTAAGCGTAGGTTCGTGAAC GGTAGATTTTCCAACGAGTCAGATACTATTGATATTACCAAGGATATGGAGAAGAC ATTAGAAATGACAGATATAAATTGGAGGGATGGGCACGATCTAAGGCAAGATATCA TTGATTACGAAATTGTTCAGCACATATTCGAGATATTCCGTCTTACAGTACAAATGC GTAACAGCTTGTCTGAGTTGGAAGATCGTGACTATGACAGGTTGATATCACCGGTCT TGAACGAGAACAATATATTCTACGACAGCGCTAAGGCGGGAGACGCTCTGCCTAAA GACGCAGATGCCAATGGGGCGTACTGCATTGCCTTAAAAGGCTTATACGAGATTAA ACAGATCACAGAGAACTGGAAAGAGGACGGCAAGTTTTCTAGAGATAAATTGAAAA TCTCAAACAAAGACTGGTTCGATTTCATCCAAAACAAAAGATACCTTAAACGTCCGG CAGCGACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGC AGGCAGCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTT ATTCCGGGCTAA SEQ ID NO: 80 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAATGGAA CTAACAACTTCCAGAACTTTATCGGCATCTCTTCCCTCCAAAAGACACTGAGAAATG CACTGATCCCAACCGAAACGACTCAACAATTTATTGTTAAGAACGGCATCATAAAA GAAGACGAGCTTCGCGGCGAGAACCGCCAGATACTTAAGGATATTATGGACGATTA TTACCGAGGCTTTATCAGCGAAACTCTTAGCTCTATTGATGATATCGACTGGACCTC CCTCTTCGAAAAAATGGAGATACAGCTCAAGAACGGCGATAATAAAGACACCTTGA TAAAGGAACAGACTGAGTACAGGAAAGCGATCCACAAGAAATTCGCGAACGACGA CAGGTTTAAAAACATGTTCTCTGCAAAATTGATATCCGACATCTTGCCGGAATTTGT GATACACAACAATAACTATAGCGCTTCAGAGAAAGAAGAGAAGACCCAAGTAATCA AGTTGTTCAGCCGCTTCGCAACGTCTTTTAAAGATTACTTTAAGAACCGGGCCAATT GTTTCTCCGCGGATGATATTAGCTCATCAAGTTGCCATCGAATTGTCAATGATAATG CGGAGATCTTCTTCAGCAATGCGCTGGTCTACAGACGAATCGTAAAAAGTCTTTCAA ATGACGACATCAATAAGATTAGTGGAGATATGAAGGATTCCCTTAAGGAAATGAGT CTTGAAGAAATATACTCATACGAAAAGTACGGGGAATTTATTACCCAGGAGGGGAT CTCCTTCTATAACGACATCTGTGGAAAAGTAAACTCATTCATGAACCTGTACTGTCA GAAAAACAAAGAAAACAAAAATCTGTATAAACTCCAAAAATTGCACAAGCAAATAT TGTGTATAGCGGACACATCATACGAGGTTCCATATAAGTTCGAAAGTGATGAAGAA GTCTACCAATCAGTGAATGGGTTTCTGGACAACATTAGTTCCAAGCACATAGTTGAA CGACTGCGAAAGATTGGTGACAATTACAACGGCTATAATTTGGACAAGATTTATATA GTTAGCAAATTTTATGAATCCGTATCACAAAAGACTTATAGAGACTGGGAAACAATC AACACGGCACTTGAGATCCATTATAACAATATTCTTCCAGGGAACGGCAAAAGCAA GGCTGATAAGGTAAAAAAGGCCGTTAAGAATGATCTTCAAAAATCCATAACGGAGA TCAACGAACTTGTAAGTAACTACAAATTGTGCTCTGACGACAATATAAAGGCTGAA ACGTATATTCACGAGATTAGCCATATCCTGAATAACTTTGAGGCCCAAGAACTCAAG TATAACCCGGAAATACATTTGGTAGAAAGCGAGCTTAAAGCGAGTGAGCTGAAAAA CGTCCTCGATGTGATCATGAATGCTTTCCACTGGTGTAGTGTCTTTATGACTGAGGA GTTGGTTGATAAAGACAATAATTTCTACGCTGAACTGGAAGAAATTTACGACGAAAT CTATCCAGTGATCTCCCTCTATAACCTCGTTCGAAACTACGTGACGCAGAAACCTTA TTCTACAAAGAAAATTAAGTTGAACTTCGGCATTCCTACACTTGCTGACGGATGGTC CAAATCCAAAGAGTACTCAAACAACGCAATCATCCTCATGCGGGATAACCTTTATTA TTTGGGCATTTTCAACGCCAAAAACAAACCTGATAAAAAGATAATTGAAGGCAATA CGAGTGAGAACAAGGGCGACTACAAAAAAATGATATATAACTTGTTGCCAGGCCCC AACAAGATGATTCCTAAAGTTTTTCTGTCTTCTAAGACTGGAGTTGAAACTTACAAA CCCTCCGCCTACATTCTTGAAGGGTATAAACAGAATAAGCACATAAAGTCCTCAAAG GATTTCGACATTACGTTTTGCCATGACCTCATCGACTATTTCAAGAACTGTATCGCCA TACATCCGGAGTGGAAGAATTTTGGATTTGATTTCTCCGACACATCTACCTATGAAG ACATAAGCGGTTTCTACCGGGAGGTCGAGCTTCAGGGCTATAAGATAGATTGGACA TACATTAGTGAAAAAGATATCGATCTTCTGCAAGAAAAGGGACAACTTTACCTTTTT CAGATTTATAATAAAGACTTTTCAAAAAAGTCCACAGGGAACGATAATCTGCACAC CATGTATCTCAAGAATCTGTTTAGTGAAGAAAACCTTAAAGACATAGTTTTGAAGCT TAACGGAGAGGCTGAGATTTTTTTTAGAAAGTCCTCAATTAAAAACCCTATAATACA CAAGAAAGGCTCTATTCTTGTTAACAGGACATATGAAGCCGAGGAGAAAGATCAGT TTGGCAATATCCAGATTGTTCGCAAGAATATCCCGGAAAATATATATCAGGAGCTGT ATAAATACTTTAACGACAAGAGCGACAAGGAGCTGAGTGACGAGGCCGCGAAGCTT AAGAATGTAGTAGGTCACCACGAAGCAGCCACCAATATCGTCAAAGACTATAGGTA CACGTACGACAAGTACTTTTTGCACATGCCTATAACTATAAACTTCAAAGCTAATAA AACTGGGTTTATTAATGACAGGATTCTCCAATACATCGCTAAAGAGAAGGATCTGCA TGTAATTGGCATAGACAGAGGTGAGAGAAACTTGATATATGTCAGCGTAATAGACA CATGTGGCAATATCGTGGAACAGAAGTCTTTTAACATCGTCAATGGTTACGACTACC AAATTAAGTTGAAACAGCAGGAAGGCGCACGACAGATCGCACGAAAGGAATGGAA AGAGATAGGCAAAATAAAAGAAATAAAGGAGGGCTATCTCAGTCTCGTTATACACG AAATTTCAAAAATGGTTATTAAGTACAATGCAATCATAGCGATGGAGGATCTCAGTT ATGGGTTCAAAAAGGGTCGGTTTAAAGTTGAGCGCCAAGTGTACCAAAAGTTCGAG ACAATGCTGATTAACAAGCTGAACTACCTCGTCTTCAAAGATATAAGTATTACGGAG AACGGTGGCCTTCTTAAAGGCTATCAACTTACTTACATCCCGGACAAGCTCAAAAAC GTAGGGCACCAATGCGGGTGTATTTTCTATGTGCCTGCGGCATATACGTCAAAGATT GACCCAACCACAGGATTCGTAAACATATTCAAGTTTAAGGACCTCACCGTTGATGCG AAAAGGGAGTTCATTAAAAAATTTGATTCTATTCGATATGATAGTGAGAAAAATCTC TTTTGTTTCACATTTGACTATAATAATTTTATTACTCAGAATACTGTCATGAGCAAGT CATCTTGGTCAGTGTACACATACGGGGTGCGGATCAAACGCAGGTTCGTCAATGGTC GCTTCTCAAACGAATCAGACACCATTGACATCACAAAGGACATGGAAAAAACCCTT GAGATGACCGACATTAATTGGCGCGATGGTCATGATCTGCGGCAAGACATCATAGA CTACGAAATCGTCCAACACATCTTTGAGATCTTTCGCTTGACGGTCCAAATGCGGAA CTCCCTGTCCGAGCTCGAGGATAGAGATTATGATCGGCTGATATCTCCCGTGCTTAA TGAAAATAACATCTTCTACGACTCCGCCAAGGCGGGTGATGCCCTGCCGAAGGATG CGGATGCTAATGGCGCTTATTGCATTGCTCTTAAGGGGCTCTATGAGATAAAGCAGA TCACGGAAAACTGGAAAGAAGACGGTAAGTTTAGTAGAGACAAGCTGAAGATCTCA AATAAAGACTGGTTTGATTTCATACAGAACAAGCGGTACCTGAAACGTCCGGCAGC GACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGC AGCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCC GGGCTAA SEQ ID NO: 81 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAATGGCA CTAACAATTTTCAGAATTTCATCGGCATTTCAAGTCTGCAAAAAACTCTGAGGAATG CTTTGATCCCTACTGAAACCACTCAGCAATTTATAGTCAAGAACGGTATAATTAAAG AAGATGAACTCAGGGGTGAAAATAGACAAATACTCAAGGACATTATGGATGACTAT TATAGAGGCTTCATCTCAGAGACTCTCTCATCAATAGATGATATCGATTGGACTAGC CTTTTCGAGAAAATGGAGATTCAGTTGAAAAATGGTGATAACAAAGATACGTTGAT AAAGGAACAGACCGAGTACAGGAAAGCCATTCATAAGAAATTTGCTAATGACGATA GATTTAAGAATATGTTTAGTGCAAAACTGATTAGTGACATTCTGCCGGAGTTCGTTA TCCATAATAATAACTACTCTGCATCCGAAAAGGAGGAAAAGACGCAAGTTATTAAA CTGTTCAGCCGCTTCGCCACAAGCTTCAAGGACTACTTCAAAAATAGAGCCAACTGC TTTTCTGCCGACGATATATCATCATCTTCATGCCATCGGATCGTTAACGATAACGCCG AGATATTCTTCAGCAACGCCCTTGTATATCGAAGAATAGTCAAAAGTCTGAGTAATG ATGATATTAATAAAATTAGCGGTGATATGAAAGACTCCCTGAAGGAAATGTCACTG GAGGAAATTTATAGTTACGAAAAGTACGGCGAATTCATTACTCAAGAAGGCATATC CTTCTATAACGACATTTGCGGAAAGGTCAACTCATTCATGAACCTTTATTGCCAGAA GAATAAGGAGAATAAAAATCTTTACAAATTGCAAAAACTTCACAAACAAATTCTTT GCATCGCGGATACGTCCTACGAAGTTCCTTACAAATTTGAATCCGATGAGGAAGTGT ATCAGAGTGTCAATGGATTTTTGGATAATATCTCTTCAAAACATATTGTGGAGAGAT TGCGCAAAATAGGTGATAACTACAATGGCTACAACCTGGACAAGATTTATATTGTTA GCAAGTTCTATGAAAGTGTCAGTCAAAAGACCTACAGAGATTGGGAGACAATCAAC ACGGCGCTCGAAATACACTACAATAACATCCTCCCCGGCAATGGGAAGAGTAAAGC CGATAAGGTTAAAAAAGCTGTTAAGAACGACCTCCAGAAATCCATCACGGAAATAA ACGAGCTGGTTTCCAACTATAAGCTGTGTAGCGATGATAATATTAAGGCTGAGACAT ATATACATGAGATCAGCCACATTCTCAACAATTTCGAGGCACAGGAACTCAAATAC AATCCCGAGATTCACTTGGTGGAAAGTGAGTTGAAGGCGTCAGAGCTTAAGAATGT ACTTGACGTAATAATGAATGCTTTTCATTGGTGCTCCGTGTTCATGACTGAGGAACT CGTGGATAAGGATAATAACTTTTATGCGGAGTTGGAAGAGATATACGATGAAATAT ACCCGGTTATCTCACTGTATAATCTGGTCAGAAATTACGTGACCCAAAAGCCTTATA GTACAAAAAAAATAAAGTTGAACTTCGGTATTCCGACATTGGCAGATGGTTGGTCCA AAAGCAAAGAATACTCTAATAACGCCATTATATTGATGCGAGACAATTTGTATTACC TTGGGATCTTTAACGCGAAAAACAAACCGGATAAGAAGATCATCGAAGGTAATACA TCTGAGAATAAGGGGGATTACAAGAAGATGATTTATAATCTGTTGCCGGGGCCAAA CAAGATGATTCCGAAGGTCTTTCTGTCATCTAAGACAGGAGTAGAGACCTACAAACC TTCTGCGTACATTTTGGAAGGCTACAAACAGAACAAGCATATAAAATCTAGCAAGG ACTTTGATATCACGTTTTGTCATGATCTGATAGATTATTTCAAAAACTGCATCGCTAT ACATCCTGAGTGGAAGAATTTCGGCTTTGACTTTTCTGACACCAGCACATACGAAGA CATCTCAGGTTTCTACCGGGAAGTCGAGCTCCAGGGGTACAAGATTGACTGGACATA TATAAGTGAAAAAGACATCGACCTCCTCCAAGAGAAGGGCCAACTTTACCTGTTCCA GATCTATAACAAAGACTTTTCTAAAAAGTCCACGGGTAACGACAACTTGCACACTAT GTATCTGAAAAACTTGTTCTCTGAAGAGAACCTCAAGGACATCGTCCTGAAGCTTAA CGGGGAGGCGGAGATCTTCTTTAGAAAGTCCTCTATCAAAAATCCCATTATCCATAA AAAGGGCTCTATACTCGTTAATAGGACATATGAAGCGGAGGAAAAAGATCAATTTG GGAACATCCAGATCGTCCGGAAAAATATACCTGAGAATATCTATCAAGAGCTGTAC AAGTATTTTAATGATAAGTCAGACAAAGAGCTCAGTGATGAGGCGGCAAAGCTCAA GAACGTGGTGGGGCATCATGAAGCTGCGACGAACATTGTCAAAGATTATAGATACA CTTACGATAAATACTTCCTCCACATGCCGATAACGATTAACTTCAAAGCCAATAAGA CGGGGTTTATAAATGATCGGATCCTTCAGTACATTGCGAAAGAGAAAGACCTCCATG TGATCGGAATTGACCGAGGAGAAAGGAATCTGATTTACGTGTCCGTGATTGATACTT GCGGGAATATAGTCGAGCAAAAGAGTTTCAACATAGTCAACGGGTATGACTATCAG ATAAAGCTCAAACAGCAGGAAGGTGCGAGGCAAATTGCGCGCAAAGAGTGGAAGG AGATAGGCAAGATTAAAGAAATCAAGGAAGGTTATCTCAGCTTGGTGATCCATGAA ATATCTAAGATGGTTATAAAGTACAATGCCATAATAGCCATGGAGGATCTTTCCTAC GGGTTTAAGAAGGGCCGATTTAAAGTGGAGCGACAAGTTTACCAGAAGTTCGAAAC CATGTTGATTAACAAACTTAACTATTTGGTGTTCAAGGATATAAGTATAACCGAAAA CGGCGGTTTGCTTAAGGGTTATCAGCTCACGTATATTCCTGATAAACTTAAAAACGT TGGACACCAGTGTGGATGTATCTTCTACGTGCCAGCCGCTTACACTAGTAAGATAGA TCCTACCACGGGGTTTGTGAATATTTTTAAGTTTAAAGACTTGACAGTCGACGCCAA AAGGGAATTTATAAAAAAGTTTGATTCTATCCGCTACGATAGTGAAAAAAATCTCTT TTGCTTTACTTTCGACTATAACAACTTCATTACGCAGAACACTGTCATGAGTAAGTCC AGCTGGAGCGTCTACACATATGGCGTCCGAATTAAACGACGATTTGTAAACGGGCG GTTTTCAAACGAATCTGACACGATAGACATTACCAAGGATATGGAGAAGACACTTG AGATGACCGACATAAACTGGCGGGACGGTCACGATCTTCGGCAGGACATAATTGAT TACGAAATCGTCCAGCATATATTCGAAATATTTCGACTTACAGTGCAAATGCGGAAC AGTCTCTCTGAACTGGAAGATCGCGATTATGACCGGTTGATTTCTCCGGTCCTCAAT GAAAATAACATATTTTATGATAGTGCTAAGGCAGGTGATGCGTTGCCAAAGGATGC AGACGCTAATGGTGCCTATTGTATCGCGCTCAAGGGATTGTACGAGATAAAGCAAA TTACGGAGAACTGGAAGGAGGATGGTAAGTTTAGCCGAGACAAGTTGAAGATTAGC AATAAAGACTGGTTTGATTTTATCCAAAACAAGAGGTACCTGAAACGTCCGGCAGC GACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGC AGCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCC GGGCTAA SEQ ID NO: 82 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAATAACGGAA CTAATAACTTTCAAAATTTCATAGGTATTTCAAGCTTGCAGAAGACCCTGAGGAATG CCCTGATTCCAACCGAGACAACGCAGCAGTTCATAGTCAAAAATGGCATTATTAAG GAAGATGAGCTGCGGGGGGAAAACCGACAGATACTCAAGGATATTATGGACGACTA TTACCGGGGATTTATCTCAGAAACGCTGAGCAGTATTGATGACATCGATTGGACCAG TCTTTTCGAGAAAATGGAAATTCAACTTAAGAATGGTGACAATAAAGACACTCTCAT AAAGGAGCAAACTGAATACCGAAAAGCCATACACAAAAAGTTTGCCAACGATGACC GCTTTAAAAACATGTTTTCAGCTAAGCTCATTAGCGACATTCTCCCCGAGTTTGTGAT TCATAACAATAACTATAGCGCATCCGAGAAGGAGGAAAAAACCCAAGTTATCAAAT TGTTCAGTAGATTCGCTACGAGCTTTAAAGATTACTTTAAAAACCGGGCTAACTGCT TCAGTGCAGACGATATCAGCTCCTCATCCTGTCATCGCATCGTCAATGATAATGCTG AGATCTTCTTTTCTAATGCACTGGTTTACCGCAGGATAGTTAAGTCTCTTAGTAACGA CGACATCAACAAGATATCAGGAGATATGAAGGATTCCCTTAAAGAAATGAGTCTCG AGGAGATATATTCTTATGAAAAATACGGCGAATTTATTACCCAAGAGGGCATTAGTT TCTATAATGACATATGCGGAAAAGTTAATAGTTTTATGAATCTCTATTGTCAGAAGA ATAAGGAGAATAAGAACCTCTACAAATTGCAGAAGTTGCACAAGCAAATTCTGTGT ATCGCGGACACCTCTTACGAGGTCCCATATAAGTTCGAGAGTGATGAAGAAGTATA CCAGAGCGTTAATGGGTTCCTGGACAACATCTCAAGTAAACACATAGTCGAAAGGC TCCGAAAGATCGGTGATAACTATAACGGATATAATTTGGATAAAATTTATATAGTTA GCAAATTTTACGAGAGCGTCAGTCAGAAGACCTACCGGGACTGGGAGACCATAAAC ACAGCGCTGGAAATACATTATAACAACATACTGCCTGGGAACGGTAAGTCAAAGGC AGACAAGGTTAAAAAGGCTGTGAAGAATGACCTGCAAAAATCAATTACAGAAATAA ATGAGTTGGTAAGTAATTACAAACTTTGCAGCGATGATAATATAAAGGCAGAGACG TACATACATGAAATATCTCATATCCTCAACAATTTCGAAGCCCAAGAACTGAAGTAC AACCCGGAAATTCATCTTGTAGAGTCTGAGTTGAAGGCCTCCGAATTGAAAAACGTT CTTGACGTAATTATGAATGCCTTCCACTGGTGCTCAGTATTCATGACGGAAGAGCTC GTGGATAAAGACAACAATTTTTACGCTGAACTGGAAGAAATATATGACGAGATTTA CCCCGTAATTTCACTCTACAACTTGGTACGAAATTACGTTACCCAAAAGCCATACTC AACAAAAAAAATTAAACTGAACTTCGGGATACCCACCCTCGCAGATGGATGGTCAA AGTCCAAAGAGTACAGTAACAATGCAATTATCCTGATGCGAGACAACCTTTATTACC TCGGGATTTTCAACGCTAAAAATAAACCTGATAAAAAAATAATTGAGGGTAATACC TCTGAAAACAAGGGGGATTATAAAAAGATGATATACAATCTGCTGCCTGGCCCGAA CAAAATGATTCCTAAAGTCTTCTTGTCTTCCAAGACTGGAGTCGAAACCTACAAGCC AAGTGCTTATATACTCGAAGGGTACAAACAAAATAAGCACATAAAATCCAGCAAGG ATTTTGATATTACATTCTGCCACGATTTGATTGATTATTTTAAGAACTGTATAGCCAT CCACCCAGAATGGAAGAATTTTGGTTTTGATTTTAGCGATACCTCAACATATGAGGA TATCTCTGGCTTTTACCGCGAGGTAGAACTGCAAGGTTATAAGATCGATTGGACTTA TATTTCTGAAAAGGACATAGATCTCCTGCAAGAGAAAGGGCAACTTTATTTGTTTCA AATATACAACAAAGATTTTAGTAAGAAGAGTACTGGCAATGATAACCTTCACACTAT GTATCTGAAGAACCTTTTTTCTGAGGAGAACTTGAAGGACATAGTCCTTAAACTCAA TGGGGAAGCTGAAATATTCTTTCGCAAAAGCTCCATTAAAAACCCGATCATTCATAA AAAGGGTTCCATCTTGGTAAACCGCACATACGAGGCGGAAGAAAAAGATCAGTTCG GAAATATCCAGATCGTAAGGAAGAATATCCCCGAAAATATATACCAAGAGCTTTAC AAATATTTTAACGATAAGTCAGACAAGGAACTGTCAGACGAAGCAGCCAAGTTGAA GAATGTCGTAGGGCACCACGAAGCAGCTACAAACATAGTTAAAGATTATCGGTACA CCTACGATAAATATTTCCTGCATATGCCAATAACCATAAACTTCAAAGCCAACAAAA CAGGGTTCATCAATGACCGAATACTTCAGTATATAGCCAAGGAAAAAGACCTGCAT GTTATAGGAATAGATAGAGGTGAGCGCAACTTGATATATGTCAGCGTGATAGACAC CTGCGGAAATATCGTCGAGCAAAAAAGTTTCAACATTGTTAATGGCTACGATTACCA AATTAAATTGAAGCAGCAAGAGGGGGCTCGGCAAATCGCGCGAAAGGAATGGAAA GAAATCGGGAAGATTAAAGAAATTAAAGAGGGCTACCTGTCTCTTGTAATTCACGA AATATCTAAGATGGTCATCAAGTATAATGCCATTATTGCGATGGAAGATCTGTCCTA CGGATTTAAGAAAGGCAGGTTTAAAGTCGAAAGGCAGGTGTACCAGAAATTCGAGA CCATGCTGATTAATAAGCTCAACTATCTCGTATTTAAGGATATTTCTATAACTGAAA ATGGAGGGCTTCTCAAAGGATATCAACTCACATACATACCTGATAAGCTGAAGAAC GTAGGCCACCAGTGTGGATGCATATTCTATGTACCAGCTGCATACACAAGCAAGATC GATCCAACTACTGGGTTTGTCAATATCTTCAAATTTAAGGACTTGACGGTCGATGCC AAACGGGAGTTCATCAAAAAGTTTGATAGTATTCGATATGATAGTGAGAAGAACTT GTTTTGCTTCACATTTGACTACAACAATTTCATAACGCAAAATACGGTTATGTCTAA ATCCTCATGGAGCGTCTACACTTACGGAGTGAGGATAAAGCGGCGCTTCGTAAATG GCAGGTTTAGCAATGAATCCGACACGATTGACATAACCAAGGATATGGAGAAAACC CTCGAGATGACCGATATAAATTGGCGGGATGGACACGATCTGCGACAAGACATAAT CGATTATGAAATCGTGCAGCACATATTTGAGATATTCAGGCTTACGGTCCAAATGAG AAATTCCCTTTCCGAACTTGAAGACCGCGATTACGACCGACTGATAAGCCCCGTTCT GAACGAAAATAACATCTTCTACGACAGCGCTAAAGCGGGAGACGCGCTGCCGAAAG ATGCGGACGCAAATGGAGCCTATTGTATCGCCTTGAAAGGGTTGTACGAGATCAAA CAGATAACCGAGAATTGGAAGGAGGATGGGAAGTTTAGTCGAGACAAACTTAAAAT AAGCAACAAGGACTGGTTCGACTTTATTCAAAACAAACGATATCTCAAACGTCCGG CAGCGACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGC AGGCAGCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTT ATTCCGGGCTAA SEQ ID NO: 83 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAATAATGGTA CTAACAATTTTCAAAACTTTATCGGCATCTCTTCACTTCAGAAAACTCTTCGGAACGC CCTTATACCGACGGAGACAACGCAGCAGTTTATAGTTAAAAACGGGATCATTAAAG AAGATGAACTCAGAGGGGAAAACAGGCAAATATTGAAGGACATTATGGACGATTAC TACCGGGGGTTTATTTCAGAGACCCTTTCATCTATTGATGACATAGATTGGACCTCCC TTTTCGAGAAAATGGAGATACAATTGAAAAACGGCGACAATAAAGATACACTTATC AAGGAACAAACTGAGTATCGCAAGGCGATTCACAAGAAGTTTGCGAATGACGATCG CTTTAAGAATATGTTTTCTGCGAAGCTCATAAGTGACATTCTGCCTGAATTTGTCATT CATAACAACAATTATTCTGCTAGCGAAAAAGAGGAAAAAACTCAAGTCATTAAGCT TTTTAGCAGGTTCGCTACTAGTTTTAAAGACTATTTTAAGAACCGGGCGAATTGCTTT AGCGCTGACGACATATCATCCTCATCCTGTCATCGCATAGTCAATGATAATGCAGAA ATATTCTTTTCTAATGCGCTCGTGTATCGGAGAATAGTGAAAAGCCTCTCTAACGAT GACATTAACAAAATAAGCGGCGATATGAAGGATAGTCTGAAGGAAATGTCCCTCGA AGAAATATACTCATACGAGAAGTACGGAGAATTTATCACCCAGGAAGGAATTAGTT TTTACAACGACATCTGTGGTAAGGTTAACTCTTTTATGAATCTGTATTGTCAAAAGA ATAAAGAAAATAAAAATCTTTATAAGCTCCAAAAGCTTCACAAACAAATCTTGTGC ATTGCGGATACGTCATACGAAGTACCTTACAAATTTGAAAGCGACGAAGAGGTGTA TCAGTCAGTGAATGGGTTCCTTGACAATATTTCTAGCAAACATATTGTGGAGCGACT TCGAAAGATCGGTGATAATTACAATGGCTATAATTTGGATAAAATTTACATAGTTAG TAAGTTTTATGAATCCGTCTCACAAAAGACGTACCGAGATTGGGAGACCATCAACAC TGCTCTGGAGATTCATTACAATAATATATTGCCTGGGAATGGGAAGTCAAAGGCCGA CAAGGTTAAAAAAGCCGTAAAAAACGATCTTCAAAAGTCCATTACCGAGATAAATG AACTTGTATCCAACTATAAGTTGTGCTCTGACGATAATATTAAAGCAGAAACGTATA TCCACGAAATAAGTCACATCCTGAACAACTTCGAAGCTCAAGAGCTCAAGTATAATC CTGAAATTCATCTCGTCGAAAGCGAGCTGAAAGCATCCGAGTTGAAGAATGTGCTTG ATGTGATCATGAACGCATTCCATTGGTGCAGTGTGTTCATGACCGAAGAACTTGTAG ACAAAGACAACAACTTCTACGCTGAATTGGAAGAGATTTACGATGAAATTTACCCC GTGATATCCCTCTATAATCTGGTAAGAAATTACGTCACGCAAAAACCATACAGTACC AAGAAAATAAAGCTCAACTTTGGTATTCCGACGTTGGCAGATGGGTGGAGTAAGAG CAAGGAGTATTCTAACAATGCAATCATCCTCATGCGCGACAATTTGTATTATCTGGG GATCTTCAACGCGAAAAATAAGCCCGACAAAAAGATAATAGAAGGCAATACGTCCG AGAACAAAGGGGACTATAAGAAAATGATTTATAACCTTCTTCCAGGACCCAACAAG ATGATCCCAAAGGTTTTCTTGAGTTCAAAAACCGGCGTAGAAACTTATAAACCGTCC GCCTACATTCTGGAAGGGTACAAGCAAAACAAGCACATTAAGTCATCTAAGGATTT CGACATTACTTTTTGTCATGATTTGATAGACTACTTCAAAAATTGTATAGCGATACAT CCGGAATGGAAAAATTTTGGGTTCGATTTTTCCGACACAAGTACTTATGAAGACATC TCAGGGTTTTATAGGGAAGTTGAACTGCAAGGTTACAAAATAGACTGGACTTATATT AGTGAGAAGGACATTGATTTGCTCCAGGAAAAGGGTCAATTGTATCTGTTCCAGATA TATAACAAGGATTTCTCTAAAAAATCTACAGGTAACGACAATCTCCACACGATGTAC CTCAAGAATCTCTTCAGCGAAGAGAATTTGAAGGATATCGTACTTAAGCTCAATGGA GAAGCGGAAATATTCTTCAGAAAGTCCAGCATTAAGAATCCTATAATTCACAAGAA AGGGTCAATTCTCGTAAACCGGACTTATGAGGCCGAAGAAAAAGATCAGTTTGGTA ACATTCAGATTGTACGGAAAAACATTCCCGAGAACATCTATCAAGAACTGTATAAAT ACTTTAATGATAAATCCGACAAGGAACTTTCTGACGAGGCTGCAAAATTGAAGAAC GTAGTGGGACACCATGAGGCCGCAACCAATATAGTAAAGGATTACAGATACACTTA TGATAAGTATTTCCTCCATATGCCGATCACGATTAATTTCAAGGCGAATAAAACCGG CTTCATTAACGATCGCATTTTGCAATATATTGCGAAGGAAAAGGATTTGCACGTGAT AGGTATAGACCGGGGTGAACGAAACTTGATTTACGTCTCTGTGATCGACACATGCGG AAATATAGTTGAACAGAAGTCCTTTAATATTGTGAATGGTTACGACTACCAGATAAA ATTGAAGCAACAGGAGGGCGCAAGACAGATAGCTCGCAAAGAGTGGAAGGAAATC GGCAAGATCAAAGAAATAAAGGAGGGTTATCTTTCCCTGGTAATTCATGAAATTAG CAAGATGGTTATTAAGTATAATGCTATAATAGCTATGGAGGACCTTTCCTATGGGTT CAAGAAAGGTCGCTTCAAAGTGGAGCGACAAGTGTATCAAAAGTTCGAGACTATGT TGATAAATAAATTGAATTATTTGGTTTTTAAAGACATTTCAATAACTGAGAACGGGG GTCTCTTGAAGGGGTACCAATTGACTTATATTCCGGACAAGTTGAAGAATGTCGGAC ACCAGTGTGGTTGCATTTTCTACGTGCCTGCCGCTTACACCTCAAAAATCGATCCGA CCACTGGTTTTGTAAATATATTTAAATTCAAAGATCTCACCGTTGATGCCAAACGGG AGTTTATCAAAAAATTCGATTCCATTCGCTACGACTCTGAGAAAAACCTTTTTTGTTT CACGTTCGATTATAACAACTTTATAACCCAAAATACTGTAATGTCCAAGTCAAGTTG GTCTGTCTATACTTACGGAGTAAGGATCAAGCGCCGCTTCGTTAATGGGAGATTCTC AAACGAGTCTGATACCATAGACATAACTAAAGACATGGAAAAAACCCTGGAAATGA CGGACATCAATTGGCGAGACGGGCATGATCTTCGACAGGACATAATAGATTACGAA ATTGTTCAACACATTTTCGAGATATTTCGACTTACGGTTCAGATGAGGAATTCCCTTT CCGAATTGGAAGACCGGGATTATGATCGACTTATATCTCCCGTGCTCAATGAAAACA ATATTTTTTATGATTCAGCGAAAGCTGGGGACGCGCTGCCAAAAGATGCCGATGCCA ATGGAGCATACTGTATCGCCCTGAAGGGTTTGTATGAGATTAAGCAAATTACTGAAA ACTGGAAGGAAGATGGCAAGTTTTCTAGAGATAAGCTTAAGATTAGCAATAAGGAC TGGTTTGACTTCATTCAAAATAAAAGGTATCTTAAACGTCCGGCAGCGACCAAAAAA GCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAA AGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 84 AGCCCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAATAATGGAA CAAATAATTTTCAAAATTTTATTGGTATCAGTTCATTGCAAAAGACTTTGAGAAATG CTTTGATCCCGACTGAGACCACACAGCAGTTCATCGTCAAAAATGGCATAATCAAGG AAGACGAACTTAGGGGTGAGAATAGACAAATATTGAAGGACATCATGGATGACTAT TATAGGGGGTTCATTTCCGAAACGCTCAGTAGTATTGATGACATTGACTGGACTAGT CTTTTCGAGAAAATGGAAATTCAGCTTAAGAACGGGGACAATAAAGACACGCTGAT CAAGGAGCAAACGGAATATAGGAAGGCGATCCATAAAAAATTCGCGAATGATGATC GGTTTAAAAACATGTTTAGTGCCAAGTTGATCAGCGACATACTGCCCGAATTCGTGA TCCACAACAATAATTACAGCGCCTCCGAAAAGGAGGAAAAAACTCAGGTCATTAAA TTGTTTAGCCGATTCGCAACGAGTTTCAAAGATTATTTTAAGAACCGGGCCAACTGT TTTTCAGCGGATGATATTAGCTCCAGCAGCTGCCATCGCATAGTAAATGATAACGCT GAAATCTTTTTTAGCAACGCACTTGTCTACCGGAGGATTGTAAAATCACTGTCAAAT GATGACATTAACAAAATATCTGGAGATATGAAGGACTCACTCAAAGAAATGAGCCT GGAAGAAATATATTCATACGAAAAATACGGGGAGTTTATTACCCAGGAAGGTATCA GTTTTTATAATGATATATGTGGAAAAGTTAATTCATTTATGAATCTTTACTGTCAAAA AAATAAGGAGAACAAGAATTTGTACAAGCTCCAAAAACTTCATAAACAGATTCTGT GCATCGCAGACACAAGTTATGAGGTACCGTACAAATTTGAGAGCGACGAAGAAGTT TATCAGAGTGTGAATGGTTTCCTGGACAATATCTCTTCTAAACACATTGTTGAGAGG CTTAGGAAGATCGGTGATAATTATAACGGCTATAATCTGGACAAAATTTATATTGTA TCAAAGTTTTATGAATCAGTCTCTCAAAAGACGTATCGGGATTGGGAAACAATTAAC ACGGCTCTGGAGATCCACTACAATAACATTCTGCCCGGCAACGGGAAGAGCAAAGC TGATAAGGTCAAGAAGGCAGTCAAGAACGACCTTCAGAAGAGCATAACAGAAATTA ACGAATTGGTCAGTAACTACAAACTGTGTAGTGATGACAACATAAAAGCCGAAACA TACATCCATGAAATAAGCCATATCCTGAATAACTTCGAAGCCCAAGAACTTAAATAC AATCCCGAGATTCATCTTGTCGAATCAGAACTCAAGGCGTCCGAGCTCAAAAATGTC CTTGACGTGATAATGAATGCCTTCCACTGGTGCAGCGTATTCATGACGGAGGAGTTG GTAGATAAAGACAACAACTTTTATGCCGAATTGGAAGAGATTTATGATGAGATTTAC CCCGTTATTTCTCTGTACAACTTGGTTCGAAACTACGTAACACAAAAACCATACTCA ACCAAAAAGATCAAACTCAATTTTGGCATACCTACATTGGCTGATGGTTGGTCCAAG TCAAAGGAATATAGCAATAATGCAATAATTCTCATGCGAGATAACTTGTATTATTTG GGGATCTTTAACGCTAAGAACAAACCAGATAAAAAGATAATCGAGGGGAACACAA GTGAGAACAAGGGTGATTACAAAAAAATGATTTACAATCTGCTTCCTGGGCCTAAC AAAATGATTCCGAAGGTGTTTCTTAGCTCTAAAACTGGAGTGGAGACGTATAAGCCT TCCGCGTACATTCTCGAAGGCTACAAGCAAAATAAGCATATCAAGTCCAGTAAGGA CTTCGACATCACTTTTTGCCACGATCTCATCGATTACTTTAAGAACTGTATCGCAATA CACCCCGAGTGGAAAAACTTTGGTTTTGATTTTTCAGACACTAGTACCTACGAGGAC ATTTCCGGCTTCTATCGAGAAGTCGAACTCCAGGGCTACAAAATCGATTGGACGTAC ATTTCTGAGAAGGACATCGACTTGCTCCAAGAGAAAGGTCAACTTTACCTCTTCCAA ATTTACAATAAAGACTTTTCAAAGAAGAGCACCGGTAATGACAACTTGCATACCATG TATCTGAAGAACCTGTTTTCTGAGGAGAACCTCAAGGATATTGTATTGAAGTTGAAT GGCGAAGCAGAAATATTTTTCCGAAAGTCATCTATCAAGAACCCCATTATACACAAA AAAGGCTCTATCCTGGTGAACCGGACTTACGAGGCAGAGGAGAAGGATCAATTCGG AAACATACAGATAGTCCGCAAAAACATCCCTGAGAATATCTATCAGGAACTCTATA AGTACTTCAATGATAAATCAGACAAGGAGCTTAGCGACGAAGCAGCTAAACTTAAA AACGTGGTTGGCCATCACGAGGCCGCTACCAACATAGTCAAAGACTACCGCTATACT TATGACAAGTACTTTTTGCACATGCCCATAACAATTAATTTCAAAGCTAACAAAACA GGGTTTATAAATGACAGAATCCTCCAATACATCGCCAAAGAGAAGGACCTCCATGT AATCGGGATTGATAGAGGCGAACGGAACTTGATTTACGTTAGTGTCATTGATACCTG TGGTAACATTGTCGAACAAAAGTCATTCAACATAGTCAATGGATATGATTATCAGAT AAAACTCAAGCAACAAGAAGGCGCGAGGCAGATTGCCAGGAAGGAATGGAAAGAA ATCGGGAAGATCAAGGAGATCAAGGAGGGTTACCTGTCCTTGGTGATACACGAGAT TTCAAAAATGGTTATAAAATACAATGCCATTATCGCGATGGAGGATTTGTCTTATGG ATTTAAGAAGGGGAGGTTCAAAGTCGAACGACAAGTCTATCAGAAGTTTGAAACAA TGCTCATTAACAAGCTCAATTACCTTGTTTTCAAGGATATAAGCATCACTGAAAACG GCGGACTCCTTAAGGGATATCAGCTGACTTATATCCCCGACAAGCTCAAGAACGTAG GGCACCAATGCGGATGCATCTTTTACGTGCCTGCAGCATATACTTCAAAAATTGATC CGACTACTGGCTTTGTTAACATTTTCAAGTTCAAGGATCTGACGGTAGACGCTAAGA GAGAATTCATAAAAAAGTTTGACAGCATCAGGTACGATAGTGAAAAGAACCTTTTTT GTTTTACCTTTGACTACAATAATTTTATTACGCAAAATACAGTTATGAGCAAATCAA GTTGGAGCGTTTACACATATGGCGTTCGGATCAAGCGCAGATTCGTCAATGGTCGCT TCTCAAATGAGAGCGATACAATCGATATAACGAAGGATATGGAGAAGACGCTTGAG ATGACAGATATCAACTGGCGGGACGGACATGACCTTAGACAAGACATAATCGATTA CGAAATAGTACAGCATATCTTTGAGATTTTTAGGCTTACAGTTCAGATGCGGAACTC TCTTTCCGAACTGGAGGACCGGGATTATGATCGGTTGATCTCCCCAGTACTGAACGA AAATAATATCTTTTACGATAGCGCGAAGGCTGGTGATGCACTCCCAAAAGACGCTG ATGCGAACGGAGCTTATTGCATAGCCCTTAAAGGGCTTTACGAGATTAAACAAATA ACAGAAAATTGGAAGGAAGATGGCAAATTTTCCCGCGACAAGTTGAAGATTAGTAA CAAAGACTGGTTCGACTTCATTCAGAATAAACGCTACCTCAAACGTCCGGCAGCGAC CAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGC CCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGG GCTAA SEQ ID NO: 85 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAATAACGGTACCAA TAACTTCCAGAACTTCATCGGTATTTCTAGCCTGCAAAAGACCCTGCGTAACGCGCT GATTCCGACCGAGACTACCCAGCAATTCATCGTGAAAAACGGTATCATTAAGGAAG ATGAATTGCGCGGTGAGAATCGTCAGATTCTGAAAGATATCATGGATGACTACTATC GCGGTTTCATTAGCGAAACCCTGTCGAGCATCGATGATATCGATTGGACGAGCCTCT TCGAGAAAATGGAAATTCAACTGAAAAATGGTGACAACAAAGATACCCTGATTAAA GAACAAACGGAATACCGCAAGGCAATCCATAAAAAGTTTGCGAATGACGACCGTTT TAAGAATATGTTCTCGGCCAAGCTGATTTCCGACATCCTGCCAGAGTTCGTCATTCA CAACAACAATTACAGCGCAAGCGAGAAAGAGGAAAAGACTCAGGTCATTAAGCTGT TTAGCCGCTTTGCGACGTCCTTCAAAGACTACTTCAAGAATCGTGCGAATTGCTTTA GCGCGGATGACATCTCTAGCTCTAGCTGTCACCGTATTGTTAACGACAATGCAGAGA TTTTCTTCAGCAACGCCCTGGTGTATCGCCGTATTGTCAAGTCTCTGAGCAACGACG ACATTAACAAGATCAGCGGCGACATGAAAGACAGCCTGAAAGAAATGTCTCTGGAA GAAATCTACAGCTACGAGAAATATGGTGAGTTTATCACCCAAGAGGGCATTAGCTTC TACAATGATATCTGTGGTAAGGTTAATAGCTTTATGAATCTGTACTGCCAGAAGAAT AAAGAAAACAAGAACTTGTACAAGCTGCAAAAGCTGCATAAGCAAATTCTGTGCAT CGCCGATACTAGCTATGAAGTTCCGTACAAGTTCGAGTCTGATGAAGAGGTGTATCA GTCAGTCAACGGTTTTCTGGATAACATCAGCAGCAAGCACATCGTCGAGCGCCTGCG CAAGATTGGTGACAACTACAATGGTTATAACCTGGACAAGATCTATATCGTGTCGAA GTTTTACGAGAGCGTGTCCCAGAAAACGTACCGTGATTGGGAAACGATTAACACGG CCTTGGAAATTCACTATAACAATATCCTGCCGGGCAACGGCAAGAGCAAAGCTGAC AAAGTCAAAAAAGCTGTGAAAAACGATCTGCAAAAGTCCATCACCGAGATCAACGA ACTGGTTAGCAACTATAAGCTGTGTAGCGACGACAACATTAAAGCTGAAACGTATA TCCACGAAATCAGCCACATCCTGAATAACTTTGAGGCACAAGAACTGAAATACAAT CCTGAGATCCATCTGGTAGAGAGCGAGCTGAAGGCAAGCGAGTTGAAAAACGTTCT CGACGTTATCATGAATGCTTTCCACTGGTGTAGCGTGTTTATGACCGAAGAACTGGT TGACAAAGATAACAATTTCTATGCAGAGCTGGAAGAAATCTATGATGAAATCTACC CGGTCATCAGCCTGTATAACCTGGTTCGTAACTACGTGACGCAGAAGCCGTACAGCA CCAAAAAGATCAAGCTGAACTTCGGTATTCCGACCTTGGCGGACGGTTGGAGCAAA TCCAAAGAATACTCCAATAATGCGATTATTCTGATGCGTGATAATCTGTACTATCTG GGTATCTTCAATGCGAAGAACAAGCCAGATAAAAAGATTATTGAAGGCAACACCAG CGAGAATAAAGGCGACTACAAGAAAATGATCTACAACTTATTGCCGGGTCCGAACA AGATGATCCCGAAAGTTTTTCTGAGCAGCAAGACCGGCGTTGAAACCTATAAGCCG AGCGCGTACATTTTAGAGGGCTATAAACAAAACAAGCACATCAAGAGCAGCAAAGA TTTTGATATTACGTTCTGCCACGACCTGATCGACTATTTCAAGAATTGTATTGCGATT CACCCTGAGTGGAAGAACTTCGGTTTTGACTTTTCCGATACCTCCACCTATGAAGAT ATTAGCGGTTTTTACCGTGAAGTCGAGTTGCAGGGTTATAAGATTGATTGGACTTAC ATTTCCGAGAAAGACATCGACCTGTTGCAAGAGAAAGGTCAGCTGTACCTGTTTCAG ATCTATAACAAAGATTTCAGCAAAAAGTCGACGGGCAATGATAATCTGCACACCAT GTATCTGAAAAACCTGTTTAGCGAAGAGAACCTGAAAGACATTGTTCTTAAGCTGAA TGGTGAGGCCGAGATCTTCTTCCGTAAAAGCTCCATTAAGAACCCGATTATCCACAA AAAGGGCTCTATTCTGGTTAACCGCACGTACGAAGCGGAAGAGAAAGATCAATTTG GTAACATCCAGATCGTGCGTAAGAATATCCCGGAGAACATTTACCAAGAACTGTAT AAGTATTTCAATGACAAGAGCGATAAAGAATTGAGCGATGAAGCGGCAAAGCTGAA AAACGTCGTTGGCCACCACGAAGCCGCGACGAATATCGTGAAAGATTATCGTTACA CCTACGACAAGTACTTTCTGCACATGCCGATCACCATCAATTTCAAAGCGAATAAAA CGGGTTTTATCAATGACCGTATCCTGCAGTACATTGCGAAAGAAAAAGATTTACACG TGATTGGTATTGATCGCGGCGAGCGCAATCTGATTTACGTCAGCGTTATCGACACGT GCGGCAATATTGTGGAGCAGAAAAGCTTCAATATCGTCAATGGTTACGACTACCAG ATCAAACTGAAGCAACAAGAGGGCGCCCGCCAGATTGCGCGTAAAGAGTGGAAAG AAATCGGTAAGATTAAAGAAATCAAGGAAGGCTACCTGTCCCTGGTGATCCATGAA ATCAGCAAAATGGTGATCAAGTACAACGCTATCATTGCGATGGAAGATCTGAGCTA CGGTTTTAAAAAGGGTCGCTTCAAAGTTGAGCGTCAAGTGTATCAGAAATTTGAGAC TATGCTGATTAACAAGTTGAACTATCTGGTTTTTAAAGACATCAGCATTACCGAGAA TGGTGGCCTGCTGAAGGGTTATCAACTGACCTATATTCCTGACAAGTTGAAAAATGT TGGTCATCAGTGTGGTTGCATTTTCTACGTACCGGCAGCGTACACGAGCAAGATTGA CCCGACCACGGGTTTCGTTAACATTTTCAAGTTTAAAGATTTGACCGTGGACGCCAA GCGTGAGTTCATTAAAAAGTTCGACAGCATCAGATACGACTCTGAGAAGAATCTGTT CTGCTTTACGTTCGACTACAATAACTTCATTACCCAAAATACCGTTATGAGCAAAAG CTCCTGGAGCGTGTACACGTACGGCGTCCGTATCAAGCGTCGTTTTGTGAATGGTCG CTTTTCCAACGAATCTGACACCATTGACATTACCAAAGATATGGAAAAGACCCTTGA GATGACCGACATTAATTGGCGTGATGGCCATGACTTGCGCCAAGACATTATCGACTA CGAAATTGTTCAGCACATCTTTGAGATTTTTCGTCTGACGGTCCAGATGCGCAACTC GCTGAGCGAGTTGGAAGATCGTGACTATGACCGTCTGATTAGCCCGGTGCTGAATGA AAACAATATCTTCTATGATAGCGCAAAGGCCGGTGACGCGCTGCCGAAAGATGCGG ATGCTAACGGTGCATACTGCATTGCACTGAAGGGTCTGTACGAAATCAAACAGATC ACCGAGAATTGGAAAGAGGATGGTAAGTTTAGCCGTGATAAGCTGAAGATTAGCAA TAAAGACTGGTTCGACTTTATTCAAAACAAGCGCTATCTGAAACGTCCGGCAGCGAC CAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGC CCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGG GCTAA SEQ ID NO: 86 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAACGGAACAA ATAATTTTCAGAACTTTATTGGGATCAGTTCGCTTCAGAAAACGCTTCGTAATGCTCT GATTCCCACAGAAACCACTCAGCAGTTTATCGTAAAGAATGGCATTATCAAGGAGG ATGAATTACGCGGCGAGAACCGCCAAATCTTAAAAGATATCATGGACGACTACTAC CGCGGTTTCATTAGCGAAACTCTTAGTTCAATTGACGACATTGACTGGACGTCCTTG TTCGAAAAGATGGAGATTCAATTAAAGAACGGTGATAACAAGGATACGTTGATTAA AGAACAGACGGAGTACCGTAAGGCTATCCACAAAAAATTTGCAAACGACGACCGCT TTAAAAATATGTTTAGCGCAAAATTAATCTCCGACATCCTGCCTGAATTCGTCATCC ATAACAATAACTATAGCGCCTCGGAAAAAGAAGAAAAAACGCAGGTTATTAAACTT TTCTCGCGCTTTGCAACAAGCTTTAAGGATTACTTCAAAAATCGCGCCAATTGTTTTT CAGCCGACGACATTAGCTCCAGTTCCTGCCACCGTATTGTGAATGACAACGCTGAGA TTTTTTTTTCCAATGCGCTGGTTTATCGTCGTATTGTTAAGAGCCTTAGTAACGACGA CATTAATAAAATTAGCGGTGATATGAAGGATAGCTTGAAAGAAATGAGTCTGGAAG AGATCTATAGTTACGAGAAGTACGGCGAATTTATTACCCAGGAGGGCATTTCATTTT ACAATGATATCTGTGGAAAAGTCAACTCCTTTATGAACTTGTATTGCCAAAAGAATA AAGAAAACAAAAACCTGTACAAACTGCAAAAGTTACACAAGCAGATTTTGTGTATC GCAGACACGTCATACGAAGTACCGTACAAGTTTGAGTCCGATGAAGAAGTGTACCA AAGCGTTAATGGCTTTTTGGATAACATTTCGAGCAAACATATCGTAGAGCGTTTGCG TAAGATTGGTGATAATTACAACGGTTACAATTTAGACAAAATCTATATCGTCTCTAA GTTTTACGAAAGTGTTTCTCAGAAAACTTACCGCGATTGGGAGACGATCAACACTGC GCTGGAGATTCATTACAATAATATCCTTCCAGGTAACGGTAAAAGCAAAGCTGATA AGGTGAAAAAGGCGGTTAAAAATGACCTTCAAAAGTCTATCACAGAAATCAACGAA TTGGTCAGCAATTATAAGCTTTGCAGTGACGATAACATTAAGGCCGAGACTTACATC CATGAGATCTCTCACATTCTTAATAATTTTGAAGCGCAAGAGCTGAAATACAATCCT GAAATCCATCTGGTCGAAAGTGAATTAAAAGCCTCCGAATTAAAAAATGTCTTGGA CGTGATCATGAATGCGTTCCATTGGTGCTCAGTTTTTATGACGGAAGAGTTGGTGGA CAAAGACAACAATTTTTACGCCGAGCTTGAGGAAATTTACGACGAAATTTACCCCGT TATTTCGTTATACAACCTTGTGCGTAATTACGTTACACAAAAGCCCTATTCGACAAA GAAAATCAAGTTAAATTTCGGGATTCCCACATTAGCTGATGGATGGTCCAAATCCAA AGAATACTCGAATAACGCTATCATCCTTATGCGTGATAATTTGTACTACTTAGGCAT CTTCAATGCGAAGAACAAACCTGACAAGAAAATTATCGAAGGAAACACTTCGGAGA ACAAAGGTGATTATAAAAAGATGATCTACAACTTGCTTCCCGGGCCAAACAAAATG ATTCCCAAGGTATTTTTGAGTTCTAAAACCGGTGTCGAAACTTACAAACCAAGTGCT TATATTTTGGAAGGATACAAACAGAACAAACATATCAAGTCTTCGAAAGACTTCGAT ATTACGTTCTGCCACGATCTGATCGATTACTTCAAGAACTGTATTGCTATTCACCCCG AGTGGAAGAACTTTGGATTTGATTTCTCCGACACGTCCACTTATGAAGATATCTCTG GCTTCTATCGCGAGGTTGAATTACAAGGGTATAAGATTGACTGGACTTATATTTCGG AGAAGGATATCGATCTTTTGCAAGAAAAAGGGCAACTTTATTTATTTCAGATCTATA ACAAGGACTTTTCAAAAAAGAGCACTGGAAATGACAATCTGCATACCATGTACCTT AAGAACCTGTTCTCGGAAGAGAACCTGAAGGACATTGTACTTAAACTGAATGGAGA GGCAGAGATCTTCTTTCGCAAATCAAGCATTAAGAACCCAATTATTCACAAAAAGG GGAGTATCTTAGTAAATCGCACATATGAGGCTGAGGAAAAAGATCAGTTTGGTAAC ATTCAGATCGTGCGTAAGAACATTCCTGAAAATATCTATCAGGAACTTTATAAGTAT TTCAACGATAAAAGTGATAAAGAGCTGAGTGACGAAGCGGCTAAACTTAAGAATGT TGTGGGACACCATGAGGCAGCAACCAATATTGTGAAGGATTATCGCTATACGTACG ACAAATACTTTTTACACATGCCCATCACTATTAATTTTAAAGCTAATAAGACTGGCTT CATTAACGATCGCATCCTGCAGTACATTGCTAAGGAAAAGGATCTTCACGTTATCGG TATCGATCGCGGGGAGCGTAATCTTATCTACGTCTCTGTCATTGACACGTGTGGCAA TATTGTGGAGCAAAAGTCCTTCAATATTGTTAACGGCTATGACTATCAGATTAAATT GAAACAGCAGGAAGGTGCGCGTCAGATTGCCCGCAAGGAATGGAAGGAAATTGGC AAGATCAAAGAAATTAAGGAGGGCTACTTAAGCTTAGTAATTCACGAAATTAGTAA AATGGTTATCAAATACAACGCCATCATCGCGATGGAGGATCTTTCGTACGGGTTTAA GAAAGGTCGTTTTAAAGTGGAGCGTCAGGTGTACCAGAAATTTGAAACTATGCTTAT TAACAAACTTAACTACCTGGTTTTCAAGGATATCAGTATTACTGAAAACGGGGGGCT GTTAAAAGGGTATCAATTAACTTACATTCCAGACAAATTAAAGAACGTTGGACATCA GTGTGGCTGCATTTTTTATGTACCAGCTGCATACACTTCAAAGATCGATCCTACGACT GGGTTCGTGAACATTTTTAAGTTTAAAGACTTGACGGTAGATGCCAAGCGCGAATTC ATCAAGAAATTCGACAGCATTCGCTACGACTCTGAGAAAAATCTTTTCTGTTTCACA TTCGATTATAACAATTTCATTACGCAGAACACAGTAATGTCCAAGTCTTCTTGGAGT GTTTATACATATGGTGTCCGCATTAAGCGCCGTTTCGTCAACGGCCGCTTCAGTAAT GAGAGCGATACTATTGACATCACAAAAGACATGGAAAAAACACTGGAAATGACCGA CATCAATTGGCGTGACGGCCATGACTTACGTCAGGATATCATTGATTATGAGATCGT TCAACACATCTTCGAAATCTTTCGCTTGACTGTTCAAATGCGCAATTCCTTGTCGGAA TTGGAGGACCGTGATTATGACCGCTTAATTTCCCCCGTCTTAAATGAAAACAATATT TTTTATGACTCTGCAAAAGCTGGAGATGCTCTGCCGAAAGACGCCGATGCAAATGG GGCATATTGCATTGCTTTAAAGGGGCTTTACGAGATCAAGCAAATCACCGAAAACTG GAAAGAGGATGGAAAGTTTTCGCGTGATAAACTGAAGATCTCTAACAAAGACTGGT TCGACTTTATCCAGAACAAGCGTTATTTGAAACGTCCGGCAGCGACCAAAAAAGCC GGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAAGA AACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 87 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAACGGCACCA ATAACTTCCAAAACTTCATCGGGATCTCTAGCCTTCAGAAGACGCTTCGCAATGCTC TTATCCCAACTGAGACCACTCAACAATTTATTGTGAAGAATGGAATTATTAAAGAGG ACGAACTGCGTGGCGAGAATCGTCAGATCTTAAAGGACATTATGGATGATTATTACC GTGGATTCATCTCCGAAACATTATCGTCGATCGATGATATCGATTGGACTTCTCTGTT CGAGAAAATGGAAATTCAATTGAAAAACGGAGATAATAAAGATACGCTTATCAAAG AACAGACGGAATATCGTAAAGCGATTCATAAGAAATTCGCAAATGACGATCGTTTC AAAAATATGTTCAGTGCCAAGCTTATTTCGGACATTTTACCTGAATTTGTAATTCATA ATAATAACTACTCAGCAAGTGAGAAGGAGGAGAAAACCCAAGTTATTAAACTGTTC TCTCGTTTCGCAACGTCCTTTAAAGATTACTTTAAAAACCGCGCGAATTGCTTTAGCG CTGACGACATTTCCAGCTCATCCTGTCATCGCATCGTAAACGACAATGCGGAAATCT TCTTCAGCAACGCCCTGGTTTACCGCCGCATCGTCAAAAGCTTATCGAATGACGACA TCAATAAGATCTCAGGAGATATGAAGGACTCGCTTAAGGAGATGTCTCTGGAGGAA ATTTATAGTTACGAAAAGTATGGAGAGTTCATTACCCAGGAGGGAATCTCGTTCTAC AATGACATTTGCGGGAAGGTGAACTCCTTCATGAACTTATACTGCCAGAAAAACAA AGAGAACAAAAATCTGTATAAATTGCAGAAATTACATAAACAGATTCTTTGTATTGC TGACACTTCCTACGAAGTACCCTATAAATTCGAGTCAGATGAAGAAGTATACCAGTC CGTGAACGGATTTCTGGACAATATCTCCTCAAAACACATCGTGGAACGCTTACGTAA AATTGGCGATAATTATAATGGTTACAATCTTGACAAAATTTATATCGTATCTAAATTT TACGAGAGTGTGAGCCAAAAGACCTACCGCGACTGGGAGACCATCAACACAGCTTT AGAAATTCACTATAATAATATCTTACCCGGCAATGGTAAGAGCAAGGCTGACAAGG TAAAAAAGGCCGTCAAGAATGATTTGCAGAAATCTATTACAGAAATTAATGAGTTA GTCTCCAACTATAAGCTTTGTTCCGACGATAACATCAAAGCTGAGACATATATTCAT GAGATTAGTCACATTCTTAACAACTTCGAGGCCCAGGAACTTAAGTACAATCCTGAA ATTCATCTTGTCGAGTCTGAGCTGAAAGCTAGTGAATTGAAAAATGTTTTAGACGTT ATTATGAACGCATTCCACTGGTGCTCTGTGTTTATGACAGAAGAACTGGTCGACAAG GACAATAACTTCTATGCCGAACTTGAGGAAATCTACGATGAAATTTACCCTGTAATC TCCTTGTATAATCTTGTACGTAATTACGTCACTCAAAAACCTTACAGCACGAAAAAA ATTAAATTGAACTTCGGGATTCCTACACTTGCCGACGGGTGGTCTAAATCCAAGGAA TATAGCAACAATGCCATTATTTTAATGCGCGACAATCTTTACTATTTAGGAATTTTTA ACGCTAAGAACAAGCCCGATAAAAAGATTATTGAAGGAAACACGTCTGAAAATAAG GGCGACTACAAAAAGATGATTTATAACCTTTTGCCCGGTCCAAACAAAATGATCCCA AAGGTATTCCTGTCATCCAAAACAGGGGTTGAGACATATAAGCCCAGCGCATATATT CTGGAAGGATACAAACAGAATAAACATATCAAAAGCAGCAAAGATTTTGACATTAC TTTTTGCCACGATTTAATCGACTACTTCAAAAACTGTATCGCTATCCACCCTGAATGG AAGAATTTCGGATTTGATTTCTCAGATACAAGTACGTATGAGGATATCAGCGGTTTC TATCGCGAAGTTGAACTTCAAGGGTATAAAATTGACTGGACCTACATTAGTGAGAA GGACATCGACCTGTTACAGGAAAAAGGCCAATTGTACTTGTTTCAGATCTACAATAA GGATTTCTCAAAAAAATCGACCGGCAATGATAACTTGCACACCATGTACCTGAAGA ACCTTTTTTCGGAGGAAAACCTTAAAGACATTGTCCTGAAGTTGAATGGAGAAGCGG AGATTTTCTTTCGTAAGTCTTCCATTAAAAATCCAATTATTCATAAGAAGGGCAGCA TCCTTGTGAACCGTACGTACGAGGCGGAAGAGAAGGACCAATTCGGTAACATTCAA ATCGTCCGCAAGAACATCCCTGAAAATATTTATCAGGAGCTTTACAAGTATTTCAAT GATAAGTCCGACAAGGAATTATCAGATGAGGCTGCGAAGTTGAAAAATGTTGTTGG TCATCACGAGGCGGCGACGAATATTGTAAAGGATTATCGCTACACTTATGACAAGTA CTTTCTGCACATGCCGATCACCATTAATTTCAAGGCGAACAAAACAGGATTTATTAA TGACCGCATCTTACAATACATTGCCAAAGAAAAGGACTTACACGTTATTGGCATTGA TCGTGGAGAACGCAACTTAATCTACGTAAGCGTTATTGACACTTGCGGGAATATCGT AGAACAAAAGAGCTTCAACATCGTGAATGGTTACGATTACCAGATCAAGCTTAAGC AGCAGGAGGGAGCGCGCCAGATCGCGCGCAAGGAATGGAAGGAGATTGGTAAGAT CAAGGAAATCAAGGAAGGTTATCTGTCCTTGGTAATCCACGAAATTTCGAAAATGGT TATCAAATACAATGCTATTATTGCAATGGAGGACTTGTCCTACGGCTTTAAAAAAGG ACGCTTTAAGGTGGAGCGCCAGGTTTATCAAAAGTTTGAAACAATGCTGATTAACAA GCTGAACTATTTGGTCTTTAAAGATATCTCCATCACCGAAAATGGTGGGCTTTTGAA AGGCTATCAACTTACATATATCCCTGATAAGCTTAAGAATGTGGGTCATCAGTGCGG GTGCATTTTTTATGTTCCTGCAGCCTACACGTCCAAAATCGATCCTACAACTGGATTT GTTAATATCTTCAAATTTAAGGATCTTACCGTCGACGCGAAGCGCGAATTTATCAAG AAATTCGATAGTATTCGTTATGATTCCGAAAAAAACCTTTTCTGTTTCACCTTTGATT ATAATAACTTTATCACGCAAAATACTGTCATGAGCAAATCGAGTTGGTCTGTGTACA CTTACGGAGTACGCATCAAGCGTCGTTTTGTTAATGGGCGCTTCAGTAACGAGTCAG ACACGATTGATATCACAAAAGATATGGAGAAAACGCTGGAGATGACAGACATCAAT TGGCGCGATGGTCATGACTTACGTCAAGACATTATCGATTATGAAATTGTCCAGCAT ATCTTTGAGATCTTTCGTTTGACTGTTCAGATGCGCAACAGCCTGTCAGAATTGGAG GATCGTGACTATGATCGCCTTATTTCTCCCGTCTTAAATGAGAACAATATCTTCTACG ACTCAGCCAAGGCTGGAGATGCACTGCCAAAAGACGCCGACGCAAATGGGGCCTAC TGTATTGCATTGAAGGGGTTGTACGAGATCAAACAGATTACAGAAAATTGGAAGGA GGACGGTAAGTTCTCTCGTGATAAGCTGAAGATTTCTAACAAAGACTGGTTCGATTT CATTCAGAACAAACGTTACCTGAAACGTCCGGCAGCGACCAAAAAAGCCGGCCAGG CGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAAGAAACGTAA AGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 88 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAACGGTACCA ATAACTTTCAGAATTTCATTGGAATCAGCAGCTTACAGAAAACCCTGCGCAATGCAC TTATCCCCACTGAGACAACCCAGCAGTTCATTGTAAAGAACGGGATTATTAAAGAA GATGAGCTTCGCGGGGAGAATCGTCAGATCTTAAAGGATATTATGGACGATTACTAC CGTGGCTTCATTTCGGAGACGCTGTCGTCGATCGACGACATCGACTGGACATCCTTG TTTGAAAAGATGGAAATCCAACTGAAGAATGGCGATAACAAGGACACGTTAATCAA AGAGCAGACGGAATACCGTAAAGCTATCCACAAAAAGTTCGCTAATGACGACCGCT TTAAGAACATGTTCTCAGCAAAACTTATTAGCGATATTTTACCTGAATTTGTCATCCA CAATAACAATTACTCCGCGAGTGAAAAAGAGGAGAAAACCCAGGTGATTAAGCTGT TTTCCCGTTTTGCAACCAGTTTCAAGGACTATTTTAAGAATCGTGCTAATTGTTTCTC TGCAGACGACATTTCCTCGTCGTCCTGCCATCGCATTGTTAATGATAATGCTGAAAT CTTTTTTTCAAACGCACTTGTGTATCGTCGCATTGTCAAAAGCTTAAGTAATGACGAT ATCAATAAGATCTCAGGAGACATGAAGGACTCCCTGAAAGAAATGTCATTGGAAGA AATTTACTCTTATGAAAAGTATGGAGAATTTATTACGCAGGAGGGTATCAGCTTCTA TAACGACATTTGTGGTAAAGTGAACAGCTTTATGAATCTTTATTGTCAAAAGAATAA AGAGAACAAAAATCTGTACAAGCTGCAGAAATTGCATAAACAAATTCTGTGCATTG CAGATACTTCGTATGAGGTTCCTTACAAATTCGAGTCGGATGAGGAGGTGTATCAAA GCGTAAACGGATTTTTGGATAACATTAGTAGTAAGCATATTGTGGAACGCCTTCGCA AGATTGGTGACAACTATAACGGATACAACTTAGACAAGATCTATATTGTCTCGAAGT TTTACGAAAGTGTTTCCCAAAAGACTTATCGCGACTGGGAGACAATCAACACTGCGC TGGAAATTCACTATAACAATATCTTGCCGGGGAACGGAAAAAGTAAGGCAGATAAG GTGAAGAAAGCAGTCAAAAATGATCTGCAAAAAAGCATTACTGAAATTAACGAACT TGTGTCAAATTACAAATTGTGTTCGGATGACAATATTAAAGCGGAAACGTATATCCA CGAGATCTCGCACATTCTTAATAATTTCGAGGCGCAGGAATTAAAGTATAATCCTGA GATCCATTTGGTGGAATCAGAACTTAAAGCTAGTGAACTGAAAAATGTCCTGGACGT TATTATGAATGCATTTCACTGGTGTTCTGTCTTTATGACAGAAGAACTTGTCGACAA AGACAACAACTTTTATGCGGAATTAGAAGAGATTTACGACGAAATTTATCCCGTTAT TTCGTTATATAATTTAGTTCGTAATTACGTGACTCAGAAACCCTACAGCACAAAAAA GATTAAATTAAACTTTGGGATTCCGACTCTTGCTGATGGATGGAGCAAGTCCAAGGA GTACTCTAATAACGCCATTATCTTGATGCGTGACAACCTGTACTACCTGGGCATTTTT AACGCTAAAAACAAACCCGACAAAAAGATCATTGAAGGGAACACCTCGGAAAATA AGGGGGACTATAAAAAAATGATCTACAATCTGTTGCCAGGCCCAAATAAGATGATC CCAAAGGTTTTTTTATCTTCCAAAACTGGCGTAGAAACTTACAAGCCGAGCGCATAC ATCCTTGAAGGATATAAACAAAACAAACATATCAAAAGTTCAAAGGACTTCGATAT TACGTTCTGCCATGATTTAATCGATTATTTCAAGAATTGCATCGCGATTCACCCAGA GTGGAAAAACTTTGGGTTTGATTTTTCAGACACCAGCACTTACGAGGATATTAGTGG ATTCTATCGTGAGGTTGAACTGCAGGGCTATAAAATTGACTGGACCTATATTTCTGA AAAAGATATTGATCTGCTTCAGGAGAAAGGCCAATTGTACTTATTTCAAATCTATAA CAAGGATTTCTCCAAGAAGTCCACGGGTAATGACAACTTACACACAATGTATCTGAA GAATCTGTTTAGTGAGGAGAACTTGAAGGACATTGTGCTGAAGCTTAATGGCGAGG CCGAAATCTTTTTTCGTAAGTCCTCCATTAAAAACCCTATTATCCATAAGAAAGGGA GTATTCTTGTCAACCGCACGTATGAGGCCGAAGAAAAGGACCAATTCGGAAACATC CAAATTGTCCGTAAAAATATTCCTGAGAACATTTACCAGGAGCTTTACAAGTATTTC AACGACAAGAGTGATAAAGAACTTTCAGATGAGGCGGCGAAACTGAAGAATGTAGT GGGGCACCACGAAGCTGCCACGAATATTGTAAAGGATTACCGTTACACCTACGACA AGTACTTTTTGCATATGCCCATCACAATTAATTTTAAGGCCAATAAAACTGGTTTTAT CAACGATCGTATCTTACAGTACATTGCTAAGGAAAAAGATCTGCACGTTATCGGTAT CGATCGCGGGGAACGCAATCTGATTTATGTTAGTGTGATTGACACGTGCGGAAATAT TGTTGAGCAGAAGAGCTTTAATATCGTAAATGGATATGACTATCAAATTAAACTGAA GCAACAGGAAGGGGCCCGCCAGATTGCCCGCAAGGAGTGGAAAGAAATTGGAAAG ATCAAGGAGATTAAAGAAGGGTACCTTTCCCTTGTTATCCACGAAATCTCGAAAATG GTGATCAAGTACAATGCCATTATTGCTATGGAGGATCTGTCATATGGGTTTAAGAAA GGCCGCTTTAAGGTGGAACGTCAGGTTTACCAGAAGTTTGAGACCATGCTTATCAAT AAGCTGAATTATCTTGTCTTCAAAGACATCTCAATCACAGAGAACGGCGGGCTGTTA AAAGGATATCAGCTGACCTATATCCCCGACAAACTGAAAAATGTCGGGCACCAATG CGGCTGTATTTTCTACGTGCCCGCTGCATACACATCTAAAATTGACCCAACGACTGG ATTCGTAAATATTTTTAAGTTTAAGGATCTTACGGTAGATGCAAAGCGCGAATTTAT CAAGAAATTTGATAGTATCCGTTACGACAGCGAGAAAAACTTATTTTGTTTTACGTT CGATTATAACAACTTCATCACGCAAAATACCGTCATGTCAAAATCTTCCTGGTCAGT CTATACGTATGGCGTCCGTATCAAGCGCCGCTTCGTCAACGGGCGTTTTTCAAACGA GTCAGATACCATCGATATCACCAAAGATATGGAAAAAACATTGGAGATGACGGACA TCAATTGGCGCGATGGTCATGACTTACGCCAGGACATTATTGACTACGAAATCGTAC AACATATTTTTGAGATTTTCCGTCTGACCGTGCAAATGCGCAACTCATTATCCGAACT TGAGGATCGTGATTACGACCGCTTGATCAGTCCTGTTCTGAACGAGAATAATATTTT TTACGACAGTGCCAAGGCGGGAGACGCACTGCCCAAGGACGCTGACGCTAACGGAG CTTATTGTATTGCGTTGAAGGGACTTTACGAAATCAAGCAAATCACTGAAAACTGGA AGGAGGATGGTAAATTCTCACGCGACAAGTTGAAAATTTCGAACAAGGACTGGTTC GATTTCATCCAAAACAAGCGTTATTTAAAACGTCCGGCAGCGACCAAAAAAGCCGG CCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAAGAAA CGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 89 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAACGGGACTA ATAACTTCCAGAACTTCATCGGTATTTCATCATTACAAAAAACGCTTCGTAACGCCT TGATCCCAACAGAAACGACCCAACAATTTATTGTAAAAAACGGCATCATCAAAGAA GACGAACTGCGTGGCGAAAATCGCCAAATTTTGAAGGACATTATGGATGACTATTAT CGTGGGTTTATCTCGGAGACATTATCCTCCATCGACGACATTGATTGGACGAGTCTT TTTGAGAAAATGGAGATCCAGCTTAAAAATGGTGATAACAAGGATACATTGATCAA GGAGCAAACCGAGTACCGCAAGGCCATCCATAAGAAGTTCGCAAATGACGACCGCT TCAAAAATATGTTTAGTGCCAAATTGATCTCGGATATCCTTCCTGAGTTCGTAATTCA CAACAATAATTATAGCGCATCCGAAAAGGAGGAAAAGACTCAAGTCATTAAGCTTT TCAGTCGCTTTGCTACCTCGTTTAAGGACTATTTCAAGAACCGCGCGAACTGCTTCTC AGCGGATGACATTTCTTCCTCGTCGTGTCACCGCATCGTGAATGATAATGCGGAGAT CTTCTTTAGTAATGCCTTGGTATACCGCCGCATTGTTAAATCCCTGTCTAACGACGAT ATCAATAAGATCTCAGGAGATATGAAGGATAGCCTTAAAGAAATGTCTCTGGAAGA AATTTACTCCTATGAAAAGTACGGTGAGTTTATCACCCAAGAGGGGATTAGCTTTTA TAACGATATCTGCGGGAAGGTGAATTCGTTTATGAACCTTTATTGTCAAAAGAATAA GGAGAATAAGAACTTATATAAGCTTCAGAAACTGCATAAACAAATCTTATGCATTGC CGATACTAGCTATGAAGTTCCGTATAAATTCGAGAGCGATGAAGAAGTTTATCAGA GCGTCAATGGGTTCTTGGATAACATTTCATCAAAACACATCGTGGAACGTCTGCGTA AGATTGGGGATAACTACAACGGATATAATCTTGACAAAATTTATATTGTATCTAAAT TCTATGAGTCGGTGAGTCAAAAGACCTACCGTGATTGGGAAACAATCAATACCGCG TTAGAAATCCACTATAACAACATTCTGCCAGGGAATGGTAAAAGTAAAGCGGACAA AGTCAAGAAGGCTGTGAAGAACGATCTGCAAAAGAGTATTACAGAGATTAACGAAT TAGTCTCCAATTATAAGTTATGCTCGGACGATAACATTAAGGCGGAGACGTATATTC ATGAGATTTCGCATATTCTTAACAACTTCGAGGCACAAGAGCTTAAGTATAACCCAG AGATTCACCTTGTCGAATCGGAGCTGAAGGCATCGGAATTAAAAAATGTCTTAGATG TAATCATGAACGCGTTCCATTGGTGCAGTGTTTTCATGACTGAGGAGTTAGTTGACA AGGACAATAACTTCTACGCAGAATTAGAAGAGATCTATGATGAGATTTATCCAGTG ATTTCGCTGTATAATCTGGTACGTAATTACGTCACTCAAAAGCCCTACTCAACAAAA AAAATTAAGCTGAACTTCGGAATTCCGACTCTGGCCGACGGGTGGTCCAAGTCAAA GGAGTATTCTAATAATGCTATCATCCTGATGCGCGATAACTTATACTATTTGGGAAT TTTCAATGCCAAAAATAAACCAGATAAAAAGATTATCGAAGGTAATACAAGCGAGA ATAAGGGTGACTATAAGAAAATGATTTACAATCTTCTTCCAGGCCCTAACAAGATGA TTCCCAAAGTTTTTTTGTCCAGTAAAACAGGGGTCGAAACTTACAAGCCCAGTGCCT ATATCCTTGAAGGGTACAAGCAGAATAAGCACATCAAATCCTCGAAAGACTTTGAT ATTACATTTTGTCATGACTTAATCGATTATTTTAAGAACTGTATCGCAATCCATCCAG AATGGAAGAACTTCGGGTTTGATTTCTCTGATACTTCCACGTATGAGGATATTTCCG GGTTCTACCGCGAAGTAGAGCTTCAGGGCTATAAAATTGACTGGACATATATTTCAG AAAAAGACATCGATCTGTTACAAGAAAAAGGACAGTTGTATCTGTTTCAAATCTATA ATAAGGATTTCTCCAAAAAGTCAACTGGAAATGATAACTTACATACAATGTATCTGA AAAATCTTTTTAGTGAAGAGAATTTGAAGGATATCGTGCTGAAGTTAAATGGCGAA GCAGAGATCTTCTTCCGCAAGTCCTCGATCAAGAATCCTATCATCCACAAGAAAGGT AGTATTCTGGTTAACCGCACGTACGAGGCCGAGGAAAAAGACCAGTTCGGTAATAT CCAGATTGTACGTAAGAATATTCCTGAAAATATTTACCAGGAATTATACAAGTATTT TAACGACAAATCGGATAAGGAGCTTTCAGATGAGGCCGCAAAGTTGAAGAACGTCG TAGGACACCATGAGGCCGCTACGAATATCGTCAAGGACTACCGCTATACGTATGAC AAGTACTTCCTGCACATGCCTATTACTATCAATTTCAAAGCTAATAAAACAGGATTC ATCAATGATCGTATCCTTCAGTACATTGCCAAAGAAAAAGATCTGCACGTAATCGGA ATCGACCGTGGCGAACGTAATCTGATTTACGTATCAGTTATCGACACATGTGGTAAC ATCGTGGAGCAGAAATCTTTTAACATTGTTAACGGCTATGATTATCAGATTAAGCTT AAACAGCAGGAGGGGGCACGCCAAATCGCTCGTAAAGAATGGAAGGAGATTGGAA AGATTAAAGAGATTAAAGAGGGGTACCTTTCGCTGGTTATTCACGAAATTTCCAAGA TGGTGATTAAGTACAATGCAATCATCGCGATGGAAGATCTTAGTTACGGATTCAAAA AGGGACGCTTCAAAGTTGAGCGTCAGGTCTACCAGAAATTTGAAACGATGCTGATT AACAAATTGAATTACTTGGTATTCAAAGATATCTCAATTACTGAAAATGGTGGCTTA TTAAAGGGTTACCAGCTTACCTATATCCCGGATAAGCTGAAGAACGTGGGCCATCAA TGCGGCTGCATCTTTTACGTCCCTGCCGCATATACCTCTAAAATTGACCCCACCACCG GATTCGTAAATATTTTTAAATTCAAGGACCTGACGGTGGACGCCAAGCGCGAATTCA TCAAAAAATTCGACTCAATCCGCTATGATTCCGAAAAAAATCTTTTCTGCTTTACGTT CGATTATAATAACTTCATTACCCAAAACACGGTGATGTCAAAATCGTCCTGGAGCGT GTATACTTATGGAGTGCGTATCAAGCGCCGCTTTGTTAATGGGCGCTTCAGTAACGA AAGCGATACCATCGACATTACCAAAGACATGGAGAAGACGCTTGAAATGACGGATA TCAATTGGCGTGACGGACACGATCTTCGTCAGGATATCATCGACTACGAGATTGTGC AACATATCTTTGAGATTTTCCGTTTAACTGTTCAAATGCGTAACTCCTTGTCCGAATT GGAAGACCGTGATTACGACCGCTTGATTTCACCAGTGCTTAACGAGAATAACATCTT CTACGACTCCGCCAAAGCAGGCGATGCCCTGCCAAAGGACGCTGATGCAAATGGTG CATACTGTATCGCGTTGAAGGGCTTATACGAGATTAAGCAAATCACCGAAAATTGG AAAGAGGATGGAAAGTTCAGTCGCGATAAGCTGAAGATCTCTAATAAAGATTGGTT TGACTTTATCCAGAACAAACGTTATTTAAAACGTCCGGCAGCGACCAAAAAAGCCG GCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAAGAA ACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 90 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAACGGTACCA ATAATTTCCAAAATTTCATCGGAATCTCATCCTTGCAAAAAACCTTGCGCAATGCTTT GATCCCCACCGAAACCACGCAGCAGTTCATCGTGAAAAACGGCATTATCAAAGAGG ATGAGTTGCGCGGGGAAAACCGTCAAATTCTTAAGGATATCATGGACGATTACTACC GTGGGTTTATCAGTGAGACCCTGTCAAGCATTGACGACATTGACTGGACCAGCTTAT TTGAGAAGATGGAGATTCAATTAAAGAACGGGGACAATAAGGACACGCTTATCAAA GAGCAGACAGAATACCGTAAAGCGATTCATAAGAAATTTGCAAATGACGATCGCTT CAAGAACATGTTTTCAGCAAAATTAATCAGCGACATCCTTCCCGAATTTGTGATTCA TAATAACAACTATTCGGCTAGCGAAAAAGAGGAGAAAACTCAGGTTATTAAGCTTT TCTCGCGTTTTGCCACTTCGTTCAAAGACTATTTTAAGAATCGCGCAAACTGCTTTTC GGCTGATGATATTTCCAGTTCTAGCTGCCATCGTATCGTTAACGATAATGCTGAGAT TTTCTTCTCTAATGCCCTGGTGTATCGTCGTATCGTTAAATCTTTGAGCAACGACGAT ATTAATAAGATTTCAGGCGACATGAAGGATTCTTTAAAGGAGATGTCTTTAGAAGAG ATTTATTCCTATGAGAAATATGGCGAGTTTATCACCCAAGAAGGAATTTCGTTCTAC AACGACATCTGTGGCAAAGTGAACAGCTTCATGAATTTATACTGCCAAAAGAATAA GGAGAATAAAAATTTATATAAACTGCAGAAACTGCATAAGCAAATTCTTTGCATTGC AGACACCTCTTATGAAGTTCCTTATAAGTTTGAATCGGACGAGGAGGTATATCAGAG TGTGAACGGGTTCCTGGACAATATTTCATCCAAGCATATTGTTGAACGTTTACGCAA AATTGGAGACAATTACAATGGGTATAACCTTGACAAAATTTACATCGTGTCGAAGTT TTACGAATCGGTAAGCCAGAAGACCTATCGTGACTGGGAAACTATCAATACCGCCTT AGAAATTCATTACAACAATATTCTTCCTGGTAACGGCAAAAGCAAAGCCGATAAGG TAAAGAAGGCTGTCAAGAACGACCTGCAAAAGTCTATCACAGAGATCAACGAGTTA GTCTCTAACTACAAATTATGTTCCGACGACAATATTAAAGCCGAAACCTACATCCAT GAGATCTCACACATTCTTAACAATTTTGAGGCCCAGGAGCTGAAATATAACCCAGAA ATTCACCTTGTAGAGAGCGAATTAAAAGCCTCCGAGCTGAAGAACGTTTTGGATGTA ATCATGAACGCATTTCATTGGTGCAGCGTATTTATGACAGAGGAGTTGGTCGACAAG GACAATAACTTTTACGCCGAGCTTGAAGAAATCTACGATGAAATTTACCCGGTAATT AGTTTATATAATTTAGTTCGCAACTACGTAACTCAGAAACCCTACAGTACCAAGAAG ATTAAATTGAACTTTGGGATCCCGACACTTGCTGACGGTTGGAGTAAATCAAAAGAA TACTCCAATAATGCAATTATCCTGATGCGCGACAATCTTTACTACTTGGGGATCTTTA ACGCAAAGAACAAACCAGATAAGAAAATCATCGAGGGCAACACCAGCGAGAATAA AGGCGATTACAAGAAAATGATCTATAATCTTTTGCCGGGACCGAACAAAATGATCC CAAAGGTTTTCCTGTCGTCGAAAACGGGAGTCGAGACATATAAACCATCTGCGTACA TCTTGGAAGGTTACAAACAGAATAAGCATATTAAGTCTAGTAAAGACTTCGACATCA CCTTTTGTCATGACCTGATTGATTATTTCAAGAACTGTATTGCTATCCATCCAGAATG GAAAAACTTCGGATTTGACTTCTCCGATACTAGCACCTACGAAGACATTTCGGGTTT TTATCGCGAAGTAGAGCTTCAAGGGTACAAAATTGATTGGACATATATTAGCGAGA AAGACATTGATTTGCTTCAAGAGAAGGGACAGTTATATTTATTCCAGATCTACAACA AAGACTTCTCGAAGAAATCCACCGGTAATGATAATCTTCACACTATGTACCTGAAGA ATTTATTTTCAGAGGAAAATCTGAAGGACATTGTACTTAAACTTAATGGAGAAGCCG AAATCTTCTTCCGCAAGAGTTCCATTAAAAATCCGATTATTCATAAAAAGGGAAGTA TCCTTGTGAACCGCACGTATGAGGCCGAAGAGAAGGATCAGTTTGGGAATATTCAA ATTGTCCGCAAAAACATCCCCGAGAACATCTACCAGGAACTGTATAAATACTTTAAT GATAAATCTGATAAAGAGTTATCAGACGAGGCTGCCAAACTGAAAAACGTAGTCGG TCATCATGAGGCAGCGACCAATATTGTAAAGGACTACCGTTACACCTACGACAAGT ATTTCCTTCACATGCCGATCACGATTAATTTTAAGGCTAACAAGACCGGCTTTATCA ATGACCGCATCTTGCAGTACATCGCGAAAGAGAAAGATTTACACGTCATCGGAATT GATCGTGGAGAGCGTAATCTTATCTACGTCAGCGTCATCGACACCTGTGGAAACATT GTGGAACAAAAAAGTTTTAATATCGTAAACGGCTACGACTATCAAATTAAACTTAA ACAGCAAGAGGGAGCTCGCCAGATCGCTCGCAAAGAGTGGAAAGAGATTGGGAAA ATTAAAGAAATTAAAGAGGGTTACCTGTCGCTGGTAATTCACGAAATCTCGAAAAT GGTCATCAAATATAATGCAATTATCGCTATGGAGGATCTGTCCTACGGGTTCAAGAA GGGACGTTTTAAAGTAGAGCGCCAGGTGTATCAAAAATTCGAAACCATGTTGATCA ATAAGCTTAACTATTTGGTCTTCAAAGATATTTCGATTACGGAGAACGGAGGTTTGT TGAAAGGATATCAGCTGACGTATATCCCAGACAAGTTGAAAAACGTGGGGCATCAA TGTGGATGTATTTTCTATGTGCCCGCGGCCTACACGAGTAAGATCGATCCTACCACT GGTTTCGTCAACATTTTCAAATTTAAAGATCTTACCGTGGATGCGAAGCGCGAATTT ATTAAGAAATTTGATAGCATTCGCTATGATTCCGAAAAGAACCTGTTCTGTTTTACG TTCGACTATAACAATTTCATTACCCAAAACACGGTGATGAGCAAATCCTCTTGGTCA GTTTATACATACGGTGTACGTATCAAACGCCGTTTCGTTAACGGACGCTTTTCCAAT GAGTCTGATACAATCGATATCACGAAAGATATGGAAAAAACATTAGAGATGACTGA TATCAACTGGCGTGACGGGCACGACCTGCGTCAAGACATTATTGACTACGAGATTGT GCAGCATATCTTCGAAATCTTTCGCTTAACTGTGCAAATGCGTAACTCGTTATCCGA GTTAGAAGACCGTGACTACGATCGCCTGATTTCACCCGTCTTGAACGAAAATAACAT CTTCTACGATTCCGCGAAGGCTGGGGACGCATTGCCCAAGGACGCAGACGCGAATG GAGCGTACTGTATTGCGCTTAAAGGATTATATGAAATCAAGCAGATCACCGAAAATT GGAAGGAGGACGGGAAGTTCTCACGCGACAAACTGAAGATTTCAAATAAGGACTGG TTCGATTTCATTCAGAATAAGCGTTACCTGAAACGTCCGGCAGCGACCAAAAAAGCC GGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAAGA AACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 91 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAATAATGGTACGAA CAACTTTCAGAACTTCATCGGCATCTCCAGCCTTCAAAAGACTTTACGCAACGCATT GATTCCCACGGAGACTACGCAACAGTTTATCGTAAAAAATGGTATTATCAAAGAAG ATGAATTACGCGGGGAGAATCGCCAGATTCTTAAGGACATTATGGACGATTATTACC GTGGATTCATCAGTGAGACACTGAGCTCCATTGATGACATCGACTGGACGTCATTGT TTGAAAAGATGGAAATCCAGTTGAAAAATGGCGATAACAAAGATACATTGATTAAA GAGCAGACAGAGTACCGCAAAGCAATTCACAAGAAATTCGCCAATGATGATCGTTT TAAGAACATGTTTAGTGCCAAGCTTATTTCGGATATCTTACCCGAATTCGTGATTCAC AACAACAATTATTCGGCAAGTGAGAAAGAGGAAAAGACCCAGGTTATCAAATTGTT TTCGCGCTTCGCCACTTCGTTCAAAGATTATTTCAAGAACCGTGCAAACTGTTTCTCC GCTGACGACATCAGTTCCAGCTCATGCCACCGTATTGTAAATGACAATGCGGAGATC TTTTTCAGTAATGCCTTAGTATATCGTCGCATTGTAAAGAGCTTATCTAATGATGACA TTAACAAGATCTCGGGTGATATGAAGGACTCACTTAAGGAGATGAGTCTGGAAGAG ATCTACTCCTACGAAAAATACGGGGAATTCATCACCCAGGAGGGAATTTCATTCTAC AACGATATCTGCGGCAAAGTTAACTCCTTTATGAATCTGTACTGTCAAAAGAACAAG GAGAATAAAAACCTGTATAAATTGCAGAAACTTCATAAACAAATTTTGTGTATCGCA GACACGAGTTATGAAGTACCTTATAAATTCGAATCCGACGAAGAGGTATATCAGTCC GTAAATGGGTTCCTGGACAATATCAGTAGTAAGCACATTGTGGAACGCTTACGCAA AATTGGAGACAATTACAACGGGTATAACCTGGACAAAATCTACATCGTATCCAAATT TTATGAAAGCGTGTCTCAAAAAACTTATCGTGATTGGGAAACAATCAACACGGCTCT TGAGATCCATTACAATAACATCTTGCCGGGTAACGGCAAATCGAAGGCAGACAAAG TTAAAAAAGCAGTTAAGAACGACTTACAGAAAAGCATTACGGAGATTAACGAGTTA GTAAGTAATTACAAATTATGCTCCGACGATAATATCAAAGCTGAAACCTACATCCAT GAAATTAGCCACATTTTGAACAATTTCGAAGCGCAGGAGCTGAAATATAACCCTGA AATCCATCTGGTAGAGTCTGAGTTGAAGGCGTCAGAACTGAAAAACGTTCTTGACGT CATCATGAATGCCTTTCACTGGTGTAGTGTTTTTATGACTGAGGAGCTTGTAGATAA GGACAACAACTTCTATGCTGAACTTGAAGAGATCTACGATGAAATCTACCCCGTAAT CAGTCTGTATAATTTAGTTCGTAACTACGTCACGCAGAAACCCTATTCGACTAAGAA AATTAAGCTGAACTTTGGGATCCCTACTTTGGCAGACGGGTGGAGCAAGAGTAAAG AATACAGTAATAATGCAATTATCTTGATGCGCGATAACTTATATTACTTAGGTATTTT CAATGCTAAGAACAAACCTGATAAGAAGATTATCGAAGGAAATACGAGTGAGAATA AGGGAGACTACAAAAAGATGATTTACAACTTGCTGCCAGGGCCTAATAAGATGATT CCAAAAGTTTTTCTGTCGAGCAAGACAGGGGTTGAAACTTATAAGCCATCCGCTTAT ATCCTTGAGGGGTACAAGCAGAATAAGCATATCAAGTCCTCCAAAGATTTTGATATT ACATTTTGCCACGACTTAATTGATTACTTCAAGAACTGCATCGCAATCCATCCCGAA TGGAAGAATTTCGGCTTCGATTTCTCAGATACGTCCACGTATGAGGATATCTCAGGC TTTTACCGCGAAGTTGAGCTGCAAGGTTATAAAATTGATTGGACATACATCTCCGAA AAAGACATTGATCTTTTACAGGAAAAGGGCCAATTATACTTATTTCAAATCTATAAC AAAGATTTTAGCAAGAAGTCCACAGGTAATGATAACCTGCATACGATGTATTTGAA AAATCTTTTCAGTGAAGAGAATTTGAAGGATATCGTCCTGAAGCTGAACGGTGAGG CTGAGATCTTCTTCCGCAAATCGTCTATCAAAAACCCCATCATTCACAAAAAGGGAA GTATCTTAGTAAACCGCACTTATGAAGCGGAGGAAAAGGATCAGTTCGGGAACATC CAGATCGTGCGCAAGAACATTCCAGAAAACATCTATCAGGAACTTTACAAATATTTC AATGACAAGTCTGATAAAGAATTATCAGACGAGGCGGCGAAACTTAAAAATGTTGT TGGACACCACGAAGCAGCGACGAATATTGTAAAGGATTATCGCTACACATACGATA AATACTTTTTGCACATGCCAATCACCATTAACTTTAAGGCGAACAAGACAGGTTTCA TTAACGACCGTATTCTGCAATATATCGCAAAGGAAAAAGACCTGCACGTTATTGGGA TCGATCGTGGCGAACGCAATTTGATCTACGTAAGCGTTATCGACACTTGCGGAAATA TCGTTGAACAAAAAAGCTTTAATATCGTCAATGGATACGATTACCAAATCAAGCTGA AACAACAAGAAGGGGCACGTCAGATCGCTCGTAAAGAATGGAAAGAGATTGGTAA GATCAAAGAGATTAAAGAAGGGTATCTTTCTTTAGTAATTCACGAGATTTCGAAAAT GGTTATTAAATACAATGCGATTATTGCTATGGAAGACTTAAGCTACGGCTTTAAGAA AGGTCGCTTCAAAGTGGAGCGCCAAGTGTATCAGAAGTTTGAAACGATGTTGATTA ACAAATTAAATTACCTGGTCTTTAAGGACATCAGTATCACAGAAAATGGGGGGTTGC TTAAAGGGTACCAGCTTACATACATCCCTGATAAACTGAAAAATGTCGGTCATCAGT GCGGATGTATCTTCTATGTACCAGCAGCCTATACCAGTAAGATTGACCCTACTACTG GCTTTGTGAATATTTTTAAATTCAAGGATTTAACCGTGGACGCCAAGCGTGAATTTA TTAAAAAATTTGATTCGATTCGCTACGACAGTGAGAAAAACCTTTTCTGCTTTACCTT TGACTACAACAATTTTATTACCCAGAACACCGTAATGTCAAAGAGTTCGTGGTCTGT ATATACCTACGGTGTTCGCATCAAGCGCCGCTTCGTAAACGGGCGTTTCAGTAACGA ATCTGACACCATCGACATCACTAAAGATATGGAGAAGACATTGGAAATGACGGACA TTAATTGGCGTGATGGCCATGACTTACGTCAGGACATTATTGATTACGAAATTGTGC AGCATATCTTCGAGATTTTCCGTTTGACAGTTCAGATGCGCAACTCACTGAGTGAGT TAGAAGATCGCGATTACGACCGTCTGATCTCACCGGTCCTTAATGAAAACAACATTT TCTACGACTCAGCAAAGGCGGGTGATGCCCTGCCAAAGGATGCGGACGCTAATGGC GCCTACTGCATCGCCCTGAAAGGATTGTATGAAATTAAGCAGATTACAGAAAATTG GAAGGAAGATGGTAAATTTAGCCGTGATAAATTAAAAATCTCGAACAAGGATTGGT TCGATTTTATTCAGAACAAACGTTATTTGAAACGTCCGGCAGCGACCAAAAAAGCCG GCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAAGAA ACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 92 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAATGGAACAA ATAATTTTCAAAATTTTATCGGCATCTCAAGTCTTCAAAAAACCCTTCGCAATGCCCT GATTCCAACTGAAACAACCCAGCAATTTATCGTCAAGAACGGCATCATTAAGGAAG ACGAGTTACGCGGGGAGAACCGTCAAATCCTGAAAGATATCATGGATGACTACTAT CGTGGGTTCATTTCGGAAACCTTGTCTTCAATCGACGACATTGACTGGACGAGTCTT TTCGAGAAAATGGAAATTCAGCTTAAAAATGGAGACAACAAGGATACTCTGATTAA GGAACAGACAGAATATCGCAAAGCTATCCACAAAAAGTTCGCTAATGATGATCGTT TCAAAAATATGTTTTCTGCTAAATTGATTTCCGATATCTTGCCTGAATTTGTAATCCA CAACAACAATTATTCTGCTTCCGAGAAGGAAGAGAAGACCCAGGTCATTAAATTATT CAGCCGCTTTGCAACCAGCTTTAAAGACTACTTTAAGAATCGCGCTAACTGCTTTTC GGCGGATGACATCTCATCATCATCATGCCACCGCATTGTGAACGACAATGCGGAGAT CTTCTTTTCGAATGCGTTAGTTTATCGTCGCATTGTCAAAAGTCTTAGCAATGATGAC ATCAACAAGATCTCAGGAGACATGAAAGATTCCTTAAAGGAGATGTCTCTTGAGGA AATCTATTCGTATGAGAAATACGGCGAGTTCATTACCCAGGAAGGTATTAGTTTCTA CAATGATATCTGCGGCAAAGTAAATTCTTTTATGAATCTGTATTGCCAAAAAAACAA AGAAAACAAGAATCTTTATAAGTTACAAAAGTTACATAAGCAAATTCTGTGCATCGC TGATACATCTTATGAGGTACCCTACAAATTTGAAAGTGATGAGGAGGTCTATCAGAG TGTCAACGGCTTCTTAGACAACATCTCTTCCAAACATATCGTGGAACGCCTGCGTAA AATCGGAGATAACTACAACGGATATAACTTAGATAAAATCTACATCGTGTCCAAGTT TTATGAAAGTGTGAGCCAAAAAACATATCGTGACTGGGAAACCATTAACACCGCAT TGGAAATTCACTATAACAACATTTTGCCAGGCAACGGGAAAAGTAAGGCGGACAAA GTTAAGAAAGCAGTTAAAAATGACCTGCAAAAAAGCATCACTGAAATTAACGAATT GGTATCGAATTACAAATTATGTAGCGACGATAATATCAAAGCAGAAACTTACATTCA CGAGATTAGTCACATTTTAAATAACTTCGAGGCCCAGGAATTGAAATACAATCCCGA AATTCATTTGGTTGAATCAGAACTGAAAGCATCAGAGTTGAAAAATGTGTTAGATGT CATTATGAATGCGTTTCATTGGTGCTCTGTGTTCATGACCGAGGAACTGGTTGATAA AGATAACAACTTTTACGCTGAATTGGAGGAGATTTACGATGAGATTTACCCGGTCAT TTCGCTTTATAACTTAGTGCGCAATTATGTGACGCAGAAACCATATTCCACGAAGAA AATCAAACTTAATTTTGGCATCCCTACTCTGGCTGATGGTTGGTCGAAATCGAAAGA GTACAGCAACAACGCGATCATTCTTATGCGTGACAATCTTTACTATTTGGGCATTTTT AATGCCAAGAATAAGCCAGATAAGAAAATCATTGAGGGGAATACTTCCGAGAATAA GGGGGATTACAAAAAGATGATCTATAACTTGCTGCCCGGCCCCAACAAAATGATTC CTAAGGTTTTCTTGTCAAGCAAGACGGGCGTCGAAACATATAAGCCGTCAGCTTATA TTCTGGAAGGCTATAAACAGAATAAGCACATCAAGTCTTCCAAGGACTTTGACATCA CTTTTTGCCACGATTTGATCGACTACTTTAAGAACTGTATTGCGATTCATCCGGAATG GAAGAACTTCGGTTTCGACTTTTCCGATACCTCAACATACGAGGATATCAGCGGCTT CTACCGTGAAGTCGAGCTTCAAGGCTACAAGATCGATTGGACATATATTTCAGAGAA GGACATTGATTTGTTACAAGAGAAAGGTCAACTTTACTTATTTCAGATCTATAACAA AGACTTTTCGAAGAAATCGACAGGAAACGATAACTTACACACTATGTATTTAAAAA ATCTGTTTTCGGAGGAAAACCTGAAAGATATTGTGCTGAAACTTAACGGCGAGGCA GAGATCTTTTTCCGTAAAAGCTCAATCAAGAATCCTATCATCCATAAAAAAGGTAGT ATTCTTGTCAACCGCACATATGAAGCGGAGGAGAAGGACCAATTCGGAAACATCCA AATTGTCCGTAAGAATATTCCGGAGAACATTTACCAAGAGTTGTATAAATACTTTAA CGATAAGTCAGATAAGGAACTTAGCGATGAGGCGGCGAAGCTTAAAAACGTAGTTG GGCATCATGAAGCTGCTACCAACATTGTAAAAGATTACCGTTACACCTATGACAAGT ATTTCTTGCACATGCCCATTACGATCAATTTCAAAGCAAATAAGACAGGCTTTATCA ATGATCGCATCCTGCAGTACATTGCTAAAGAGAAGGATTTGCATGTTATCGGTATTG ATCGCGGAGAGCGCAATTTGATCTACGTCTCCGTAATCGACACTTGCGGTAACATTG TTGAGCAGAAGTCGTTCAACATCGTTAATGGTTATGATTACCAAATCAAGCTGAAGC AGCAAGAGGGTGCCCGCCAGATCGCGCGTAAGGAATGGAAAGAAATCGGGAAAAT TAAAGAGATCAAAGAAGGCTATTTGTCTCTGGTAATTCACGAAATCAGCAAGATGG TGATCAAGTATAACGCGATCATTGCGATGGAGGATCTTTCTTATGGCTTCAAGAAAG GGCGCTTTAAAGTCGAACGCCAGGTCTACCAGAAATTTGAGACAATGCTTATCAACA AGCTTAACTATCTTGTATTTAAGGATATTTCCATCACTGAGAACGGAGGACTTTTAA AGGGGTACCAACTGACGTACATTCCTGATAAGCTGAAGAACGTTGGTCATCAATGC GGATGCATCTTCTATGTGCCAGCGGCTTACACCTCCAAAATCGATCCCACTACAGGC TTTGTCAATATCTTCAAATTCAAGGATTTGACCGTTGACGCGAAGCGCGAGTTTATC AAGAAGTTTGATAGCATTCGCTACGACAGCGAAAAAAATTTATTTTGTTTTACTTTC GACTACAATAACTTTATTACTCAGAACACTGTCATGTCAAAGAGTTCGTGGAGTGTC TACACGTACGGAGTACGTATTAAGCGCCGTTTCGTCAACGGACGCTTCTCAAACGAA AGCGACACGATCGACATCACCAAAGACATGGAAAAAACTCTTGAGATGACGGATAT CAATTGGCGCGACGGCCATGACCTGCGTCAGGATATCATTGATTACGAGATCGTTCA GCACATCTTCGAAATCTTCCGCCTTACCGTCCAGATGCGCAACAGTTTAAGCGAGCT TGAAGACCGCGACTACGATCGTTTGATTAGCCCCGTTCTGAACGAGAATAATATTTT CTACGACAGCGCAAAGGCCGGTGATGCTTTGCCAAAGGACGCAGACGCGAATGGAG CCTACTGCATCGCCCTGAAGGGCTTATATGAGATTAAGCAAATTACCGAAAATTGGA AGGAAGATGGTAAGTTCTCCCGTGATAAGCTTAAAATTAGCAATAAGGATTGGTTCG ACTTCATCCAGAACAAACGTTACCTGAAACGTCCGGCAGCGACCAAAAAAGCCGGC CAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAAGAAAC GTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 93 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAACGGAACAA ACAATTTCCAAAACTTCATCGGTATCTCTTCGTTGCAGAAGACTCTGCGTAATGCTTT GATCCCGACGGAGACAACCCAACAATTTATCGTCAAAAACGGTATTATTAAGGAGG ACGAGTTACGTGGAGAAAATCGTCAAATCCTTAAGGACATCATGGACGATTATTATC GCGGGTTTATTTCTGAAACCCTGAGCAGTATCGATGATATCGACTGGACCTCACTTT TTGAGAAAATGGAGATCCAGTTGAAGAACGGTGATAACAAAGACACTCTGATCAAA GAGCAAACTGAATACCGCAAGGCAATTCACAAAAAGTTCGCCAACGACGACCGTTT CAAGAATATGTTCTCAGCTAAGTTAATCAGCGACATTTTGCCAGAGTTCGTTATCCA CAACAATAATTATAGTGCTTCAGAGAAGGAGGAAAAAACCCAAGTGATTAAACTTT TTTCGCGCTTTGCAACCTCATTCAAGGACTACTTCAAGAATCGCGCGAATTGCTTCA GTGCGGACGACATTTCTTCTTCAAGTTGCCATCGTATCGTTAACGATAACGCGGAAA TTTTCTTCTCTAATGCTTTGGTGTATCGCCGCATTGTAAAATCGCTTAGTAACGATGA CATTAATAAGATCTCAGGTGATATGAAAGATTCATTGAAGGAAATGAGCTTGGAAG AGATTTACAGTTACGAAAAATATGGAGAATTTATTACTCAGGAAGGCATCTCATTCT ATAACGATATCTGCGGGAAGGTAAATTCGTTTATGAACTTATATTGCCAGAAAAATA AAGAGAATAAAAATTTGTATAAGCTTCAGAAGTTGCACAAACAGATCCTGTGCATT GCAGACACCTCGTATGAGGTTCCGTATAAATTTGAGTCCGATGAAGAAGTGTATCAG TCTGTGAATGGTTTCTTAGATAATATCTCTTCCAAGCATATTGTCGAACGCCTGCGCA AAATTGGTGATAACTATAACGGATACAATCTGGATAAAATTTACATCGTTTCTAAAT TTTACGAGTCAGTCTCGCAGAAGACCTACCGCGACTGGGAAACAATTAACACGGCA TTGGAGATTCACTACAATAATATCTTGCCTGGTAACGGTAAGTCTAAGGCAGATAAG GTAAAAAAAGCTGTGAAAAACGACCTTCAGAAAAGCATCACGGAGATTAATGAGCT GGTGAGTAATTACAAATTATGTTCAGACGATAATATTAAAGCTGAAACGTATATCCA TGAAATCTCGCATATCTTGAACAACTTCGAGGCCCAAGAACTTAAATATAACCCCGA AATCCATTTAGTCGAGTCTGAATTGAAAGCGTCGGAATTAAAAAACGTCTTAGACGT CATTATGAACGCGTTTCACTGGTGTTCAGTTTTCATGACCGAAGAGCTGGTCGACAA AGACAACAACTTCTATGCGGAATTGGAGGAAATCTATGATGAAATCTACCCTGTTAT TTCACTGTATAACCTTGTGCGCAACTATGTCACTCAGAAGCCGTATTCGACCAAAAA AATTAAATTGAATTTCGGTATCCCTACTCTTGCAGACGGATGGAGTAAAAGCAAGGA ATACAGTAATAACGCCATTATTCTTATGCGCGACAATTTATACTACCTGGGCATCTTT AACGCAAAGAATAAGCCGGATAAGAAGATTATTGAGGGTAACACCAGTGAGAACA AGGGCGACTATAAGAAGATGATCTATAACTTATTGCCAGGTCCAAATAAAATGATC CCAAAAGTATTCTTATCATCAAAGACGGGAGTTGAAACCTATAAGCCTAGTGCCTAT ATTCTTGAGGGATATAAACAGAACAAGCACATTAAGTCGTCTAAGGATTTTGACATT ACGTTCTGCCATGACTTAATCGACTATTTTAAAAACTGTATTGCGATTCACCCCGAAT GGAAGAATTTTGGATTCGATTTTTCGGATACCTCGACCTATGAAGATATTTCGGGAT TTTATCGTGAAGTGGAGTTGCAAGGCTATAAAATCGATTGGACCTATATCTCAGAAA AAGACATTGATTTATTACAGGAAAAGGGACAACTGTACCTTTTCCAAATTTATAACA AGGACTTTTCTAAAAAGTCCACAGGAAATGATAACCTTCACACCATGTACCTGAAGA ACCTTTTCTCAGAGGAAAACCTGAAGGACATTGTCCTTAAGTTAAATGGAGAAGCG GAGATCTTTTTCCGTAAATCTAGTATCAAGAATCCGATTATCCATAAAAAAGGTTCG ATTTTGGTAAATCGCACCTATGAAGCGGAAGAGAAAGATCAATTTGGTAACATCCA GATCGTGCGCAAGAATATCCCGGAGAACATTTACCAAGAGCTGTATAAGTACTTCA ATGATAAGTCTGATAAGGAACTGTCAGATGAAGCTGCGAAATTGAAGAACGTGGTT GGGCATCATGAAGCCGCTACCAATATCGTCAAGGATTACCGTTATACCTATGACAAA TATTTCTTACACATGCCGATTACGATCAATTTTAAGGCAAACAAGACAGGATTCATC AACGACCGTATCTTGCAGTATATTGCCAAAGAGAAGGATCTGCATGTGATCGGTATT GACCGCGGGGAGCGCAATTTAATCTATGTATCGGTGATCGATACTTGTGGTAACATC GTAGAACAAAAGAGCTTTAACATCGTGAATGGTTACGACTATCAGATCAAGCTGAA ACAACAGGAAGGAGCCCGCCAGATCGCTCGCAAGGAATGGAAAGAAATCGGGAAA ATTAAGGAAATCAAGGAAGGCTACCTTTCATTGGTCATTCACGAAATTTCGAAAATG GTAATTAAGTACAACGCGATCATCGCCATGGAGGACCTTTCGTACGGATTTAAGAAG GGTCGTTTCAAAGTTGAGCGCCAGGTATACCAAAAATTCGAGACTATGCTTATCAAC AAACTTAACTACTTGGTCTTTAAGGACATTTCTATTACCGAAAACGGCGGCTTACTT AAAGGCTATCAATTGACATATATTCCCGACAAACTGAAGAATGTTGGACATCAATGC GGGTGTATTTTCTATGTGCCGGCAGCTTACACTAGTAAGATCGACCCTACAACCGGG TTCGTAAACATTTTTAAATTCAAAGACTTAACAGTCGATGCGAAGCGTGAATTTATT AAGAAGTTTGATAGTATCCGCTATGACAGTGAAAAGAACTTGTTTTGCTTTACGTTC GACTACAATAACTTTATTACACAGAACACGGTCATGTCTAAATCATCATGGTCGGTT TACACATATGGGGTGCGCATCAAGCGTCGCTTTGTAAATGGCCGTTTTAGTAATGAG AGCGACACAATCGACATCACAAAGGATATGGAGAAAACTCTTGAGATGACAGACAT CAATTGGCGTGACGGTCATGACTTACGCCAAGATATCATCGACTACGAAATCGTACA GCATATTTTTGAGATTTTTCGTCTTACTGTGCAAATGCGTAATTCTTTATCCGAACTG GAAGATCGTGATTACGACCGCTTGATTAGTCCCGTCTTAAATGAGAACAATATTTTC TATGATTCTGCGAAAGCCGGAGATGCACTGCCCAAAGACGCTGATGCCAATGGCGC GTATTGCATTGCATTAAAAGGATTATATGAGATTAAACAGATTACCGAAAATTGGAA AGAGGACGGTAAATTCTCACGCGATAAATTGAAGATTTCTAACAAGGACTGGTTCG ACTTTATCCAAAATAAACGTTATCTTAAACGTCCGGCAGCGACCAAAAAAGCCGGC CAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAAGAAAC GTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 94 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAATAACGGTACCAA CAACTTTCAGAATTTCATTGGCATTAGCTCGCTTCAAAAAACTTTACGCAATGCTCTT ATTCCGACTGAGACGACACAACAGTTTATCGTTAAGAATGGCATCATCAAAGAAGA TGAATTACGCGGAGAAAACCGCCAGATCCTGAAAGACATTATGGACGATTATTACC GTGGGTTCATCTCCGAGACGTTGTCATCGATCGATGACATCGACTGGACGTCACTTT TTGAAAAAATGGAGATCCAGTTAAAGAACGGTGACAATAAGGATACATTGATCAAA GAACAGACCGAGTACCGTAAAGCGATTCATAAAAAGTTTGCGAACGATGATCGCTT CAAGAATATGTTTTCTGCGAAATTAATTTCCGACATTTTACCTGAATTTGTTATTCAT AATAACAACTACTCGGCGTCTGAGAAAGAGGAGAAAACCCAAGTGATTAAACTTTT TTCACGTTTCGCAACGTCGTTCAAAGACTATTTTAAAAATCGTGCTAATTGCTTTAGC GCGGATGACATCAGCTCTAGTTCATGTCATCGCATTGTCAACGATAATGCTGAGATC TTTTTCAGTAATGCGTTAGTGTACCGTCGTATTGTGAAGTCCTTATCTAATGATGATA TCAATAAGATCAGCGGGGATATGAAGGACTCACTTAAGGAGATGAGCTTGGAGGAA ATCTATTCCTATGAGAAGTATGGTGAGTTTATTACGCAAGAAGGAATTAGCTTTTAC AACGATATCTGTGGAAAGGTGAATTCGTTTATGAATTTGTATTGCCAGAAAAATAAG GAGAACAAGAACCTTTATAAATTGCAAAAGTTACACAAGCAAATCCTGTGCATTGC AGATACTTCCTACGAGGTGCCTTACAAGTTTGAATCCGACGAAGAGGTCTACCAATC TGTAAACGGTTTCTTAGATAATATTAGTTCCAAGCATATTGTGGAGCGCCTTCGTAA AATTGGCGATAATTACAACGGTTACAATTTAGACAAAATTTACATTGTCAGTAAATT CTACGAGTCCGTATCTCAAAAGACGTATCGTGATTGGGAGACTATCAATACGGCCCT GGAGATCCACTACAACAATATCTTGCCCGGTAATGGTAAGTCGAAGGCCGATAAAG TTAAGAAAGCGGTGAAAAATGACTTACAGAAGTCAATCACCGAAATTAACGAATTG GTGTCCAATTATAAATTGTGTTCAGATGATAATATCAAAGCCGAGACCTACATTCAT GAGATTTCCCATATCTTAAATAATTTCGAGGCGCAAGAGCTTAAGTATAACCCAGAA ATCCACCTGGTAGAATCTGAGTTGAAGGCGTCAGAGTTAAAAAATGTTTTAGATGTC ATTATGAACGCGTTTCACTGGTGCTCCGTATTTATGACGGAGGAATTAGTAGATAAA GACAACAATTTCTATGCCGAACTTGAGGAAATCTATGATGAGATCTATCCCGTCATT AGCCTGTATAACTTGGTCCGCAACTATGTTACCCAAAAACCGTACAGTACCAAGAAG ATTAAGCTGAATTTCGGCATTCCTACACTGGCTGATGGTTGGAGTAAATCGAAGGAA TATTCGAATAACGCGATTATCTTGATGCGCGACAACTTATACTATTTGGGGATCTTTA ACGCCAAAAACAAACCGGATAAGAAGATTATTGAGGGAAACACATCAGAGAACAA AGGCGACTACAAAAAAATGATTTACAACTTGTTACCGGGGCCTAACAAAATGATCC CGAAGGTGTTCTTATCCAGTAAAACAGGCGTTGAGACCTACAAACCTTCCGCATACA TCCTGGAAGGGTATAAGCAGAACAAGCACATTAAGTCCAGCAAGGATTTCGATATT ACCTTCTGTCATGATTTAATTGACTATTTCAAGAACTGTATTGCAATCCACCCCGAGT GGAAGAACTTCGGATTCGACTTCTCAGATACGAGCACATATGAGGACATCTCGGGG TTCTATCGTGAAGTAGAACTGCAGGGATATAAAATTGATTGGACATATATTTCCGAA AAAGACATCGACCTTTTACAAGAGAAGGGTCAACTTTACTTGTTCCAAATTTACAAT AAAGACTTCTCAAAAAAAAGCACGGGTAACGATAATTTACACACTATGTATTTAAA GAACCTTTTCTCGGAAGAGAATTTAAAGGATATCGTATTGAAGTTGAATGGAGAAG CGGAGATCTTCTTCCGTAAGTCCAGTATTAAAAACCCTATTATTCACAAGAAGGGAT CGATTTTAGTTAACCGCACATACGAGGCCGAAGAGAAGGACCAATTTGGGAACATT CAAATTGTCCGCAAAAACATCCCTGAGAACATTTATCAAGAGCTTTATAAGTACTTT AACGATAAGTCCGATAAGGAATTGTCAGATGAGGCGGCAAAGTTGAAGAATGTCGT GGGGCATCATGAAGCTGCCACCAACATTGTGAAGGACTACCGCTACACTTACGACA AATACTTCCTGCACATGCCCATTACGATCAATTTTAAGGCCAATAAGACAGGCTTTA TTAACGACCGTATTCTTCAATATATCGCTAAGGAGAAGGACCTTCATGTGATTGGGA TCGACCGCGGAGAACGTAATTTAATTTATGTGTCCGTCATCGATACGTGTGGAAATA TCGTGGAACAGAAATCATTCAATATCGTGAATGGCTATGATTACCAGATCAAATTAA AACAGCAGGAGGGCGCTCGCCAAATTGCGCGTAAGGAATGGAAAGAGATCGGAAA AATCAAAGAAATCAAAGAAGGATATTTGTCATTGGTGATCCATGAGATTTCAAAAA TGGTAATTAAATATAATGCAATTATCGCAATGGAAGACCTGTCCTATGGTTTTAAGA AGGGTCGTTTCAAGGTAGAACGCCAAGTGTATCAAAAGTTCGAGACGATGCTGATC AATAAGCTGAATTATCTTGTGTTTAAGGACATTAGCATCACGGAAAATGGAGGGCTG TTGAAAGGCTATCAACTGACGTATATCCCTGACAAGCTGAAAAATGTTGGCCATCAG TGCGGGTGCATTTTCTACGTCCCCGCGGCGTATACAAGCAAGATCGATCCTACTACG GGATTCGTAAATATTTTTAAATTCAAAGACTTAACCGTGGACGCCAAGCGCGAATTC ATTAAGAAGTTTGATAGCATTCGCTACGATTCAGAAAAAAATCTTTTCTGTTTTACGT TCGATTACAACAATTTTATCACCCAGAACACAGTGATGAGCAAGTCATCCTGGTCTG TCTATACCTACGGTGTCCGTATCAAACGCCGCTTCGTCAACGGACGCTTCTCTAATG AATCTGATACCATTGACATCACCAAGGACATGGAAAAGACACTTGAGATGACAGAT ATTAACTGGCGTGACGGACATGACCTGCGTCAGGACATCATCGATTATGAGATTGTT CAGCATATCTTCGAGATCTTCCGCCTGACAGTACAAATGCGCAATTCACTGTCAGAA CTTGAAGACCGCGACTATGACCGCCTGATCTCTCCAGTATTAAATGAGAACAATATC TTTTATGACAGTGCTAAGGCCGGCGATGCCCTTCCGAAAGATGCTGATGCTAACGGA GCTTATTGTATTGCATTAAAGGGTCTTTATGAGATCAAGCAAATTACCGAGAATTGG AAGGAGGATGGCAAATTCTCGCGCGACAAACTGAAAATCAGTAACAAGGACTGGTT CGATTTTATTCAGAATAAACGTTACCTGAAACGTCCGGCAGCGACCAAAAAAGCCG GCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAAGAA ACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 95 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAATAACGGAACGA ACAACTTCCAGAACTTCATCGGCATCAGTTCTTTACAAAAAACCCTGCGTAACGCCC TTATTCCGACTGAGACAACACAACAGTTCATCGTTAAAAACGGAATTATCAAAGAG GACGAGTTGCGCGGCGAGAATCGCCAAATTTTGAAAGATATTATGGACGACTATTAT CGTGGTTTTATTTCAGAAACACTGAGTTCGATTGACGATATCGATTGGACGAGCCTG TTTGAGAAAATGGAAATCCAGTTGAAAAATGGCGATAATAAAGACACTTTAATCAA AGAACAAACCGAGTATCGTAAAGCGATCCATAAAAAGTTCGCTAATGACGATCGTT TTAAGAATATGTTCAGTGCGAAACTGATTTCAGACATTTTGCCCGAGTTCGTGATCC ATAATAACAACTATTCCGCCTCGGAAAAGGAAGAAAAAACCCAGGTGATTAAGCTG TTCAGTCGCTTCGCAACATCTTTCAAGGATTATTTCAAGAATCGCGCGAATTGCTTCA GTGCGGACGATATTTCTAGTTCAAGCTGCCATCGTATCGTTAATGATAACGCGGAGA TTTTTTTTAGCAATGCTCTGGTGTACCGCCGCATTGTTAAGTCACTGTCCAACGATGA TATTAACAAGATCTCAGGAGACATGAAAGACTCGCTTAAAGAGATGAGTCTGGAAG AGATCTATTCTTATGAGAAGTATGGCGAGTTTATTACCCAAGAAGGAATCTCATTCT ACAATGATATTTGTGGAAAGGTGAACAGCTTTATGAATCTTTACTGCCAAAAAAACA AGGAGAATAAGAATCTTTACAAACTTCAGAAGTTACATAAACAGATTTTGTGTATTG CGGATACGTCTTATGAAGTCCCCTACAAATTTGAATCGGATGAAGAGGTATACCAAA GTGTGAACGGATTCTTGGACAATATTTCTTCTAAACATATTGTTGAACGCTTACGTA AGATCGGGGATAACTACAATGGCTACAATCTTGACAAAATCTACATTGTTAGCAAAT TCTACGAGAGTGTCAGCCAAAAGACGTACCGCGATTGGGAAACAATTAATACTGCG CTTGAGATTCACTATAATAACATTTTACCAGGCAACGGCAAGTCCAAGGCGGATAA AGTTAAAAAAGCTGTTAAAAACGATTTGCAAAAATCTATCACAGAAATTAACGAGT TAGTTAGTAACTACAAACTGTGCTCCGATGACAACATTAAGGCTGAGACGTATATCC ATGAGATCTCTCACATCTTAAACAATTTTGAAGCTCAAGAACTTAAGTACAATCCGG AAATCCACCTGGTGGAATCCGAGCTGAAGGCTAGCGAACTGAAGAACGTATTGGAC GTGATCATGAACGCGTTCCACTGGTGTTCTGTCTTTATGACGGAAGAGCTTGTCGAC AAAGATAATAACTTTTACGCGGAACTTGAGGAAATTTACGATGAGATTTACCCAGTT ATTTCATTGTATAACCTTGTCCGTAATTACGTGACCCAAAAGCCTTATAGTACGAAA AAAATCAAATTAAATTTTGGAATCCCAACACTGGCTGACGGTTGGAGCAAATCTAA GGAGTATTCTAATAACGCAATCATCTTAATGCGTGACAACCTGTATTATTTGGGTAT CTTCAATGCCAAAAATAAGCCTGACAAAAAGATTATCGAAGGAAATACTTCGGAGA ATAAGGGGGATTACAAAAAAATGATTTACAATTTGCTGCCCGGGCCGAACAAGATG ATCCCCAAAGTGTTCTTATCCTCGAAGACTGGTGTAGAAACATACAAGCCAAGCGCA TACATTCTGGAGGGTTACAAGCAAAACAAACACATCAAATCTTCAAAAGACTTTGA CATTACATTTTGCCATGATCTTATTGACTACTTCAAAAACTGCATTGCTATTCACCCC GAGTGGAAGAACTTTGGGTTTGACTTCAGCGACACGTCTACGTATGAGGACATCTCC GGGTTCTACCGTGAAGTTGAGTTACAAGGGTATAAGATTGACTGGACGTATATTTCA GAGAAAGATATCGATCTTTTGCAGGAAAAGGGCCAGTTATATTTATTCCAGATTTAC AACAAGGACTTTAGTAAGAAGTCAACAGGAAATGACAACTTGCATACGATGTATTT GAAAAATCTTTTTTCTGAGGAAAATCTTAAGGACATCGTACTGAAATTGAATGGCGA GGCTGAAATCTTCTTCCGTAAATCCTCCATTAAGAATCCCATTATCCACAAAAAGGG GTCTATCCTGGTGAATCGTACCTACGAGGCAGAGGAGAAGGATCAATTCGGAAATA TTCAGATTGTTCGTAAGAACATCCCCGAGAACATTTATCAAGAATTGTATAAGTACT TTAATGACAAATCTGACAAAGAGTTATCCGACGAAGCTGCGAAACTGAAAAACGTT GTTGGTCACCACGAGGCCGCCACTAATATCGTAAAAGACTACCGTTATACCTATGAC AAGTACTTTTTGCACATGCCGATCACTATCAACTTCAAGGCGAATAAGACGGGCTTC ATTAACGATCGTATCCTGCAATACATCGCCAAGGAGAAGGACCTTCACGTCATTGGG ATTGACCGTGGTGAGCGTAACCTGATTTATGTAAGCGTCATTGATACCTGCGGTAAT ATCGTCGAACAGAAAAGTTTCAACATTGTAAATGGATATGACTATCAGATCAAACTT AAGCAGCAGGAGGGTGCACGCCAGATTGCCCGCAAGGAATGGAAGGAGATTGGGA AGATTAAGGAAATTAAAGAAGGTTACTTATCACTGGTTATTCACGAGATCAGTAAA ATGGTAATCAAATATAACGCGATCATTGCCATGGAGGATCTGAGCTATGGCTTTAAA AAGGGCCGTTTCAAAGTCGAGCGCCAGGTATATCAAAAGTTTGAAACAATGCTGAT TAACAAATTAAACTATCTGGTTTTCAAAGATATTTCGATCACTGAAAATGGCGGGCT GTTGAAGGGATACCAACTTACATACATCCCTGACAAACTGAAAAATGTCGGTCACC AATGTGGATGTATCTTTTATGTACCAGCAGCGTATACGAGCAAAATCGATCCAACTA CGGGTTTTGTGAACATCTTTAAGTTCAAGGATTTGACAGTAGATGCCAAACGCGAGT TCATTAAAAAATTTGATTCAATTCGCTACGATTCAGAGAAAAATCTTTTTTGTTTCAC GTTCGATTACAATAATTTCATTACGCAGAACACAGTAATGTCAAAGTCAAGCTGGTC GGTCTACACGTATGGAGTCCGTATTAAACGTCGTTTTGTAAACGGCCGTTTCTCAAA TGAATCAGATACAATTGATATTACGAAGGATATGGAGAAGACATTAGAGATGACTG ACATTAACTGGCGCGACGGACATGATCTTCGTCAGGACATTATTGATTATGAGATTG TACAGCATATCTTTGAGATCTTCCGCCTGACCGTTCAGATGCGCAATTCGTTGTCCGA GTTAGAAGACCGCGATTACGACCGTTTAATCAGTCCCGTCTTAAACGAAAATAACAT CTTCTACGATTCAGCCAAGGCAGGCGATGCCTTGCCAAAGGATGCTGACGCAAATG GCGCATACTGTATTGCGTTGAAAGGCCTTTATGAAATCAAGCAAATTACCGAAAACT GGAAAGAAGACGGAAAATTCTCCCGTGATAAGTTGAAAATCTCTAATAAGGATTGG TTCGATTTCATCCAAAATAAACGCTATTTGAAACGTCCGGCAGCGACCAAAAAAGCC GGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAAGA AACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 96 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAACGGAACTA ATAATTTCCAAAATTTTATAGGCATCTCTTCTTTACAGAAGACTCTTCGTAACGCCCT AATCCCGACTGAGACCACACAACAATTCATAGTGAAAAATGGGATCATTAAAGAAG ACGAGCTGCGTGGGGAGAACAGGCAGATCCTAAAAGACATAATGGACGATTATTAT AGAGGGTTCATCTCAGAGACATTATCTAGCATCGACGACATTGACTGGACCTCCCTG TTTGAAAAAATGGAAATCCAGCTGAAGAATGGTGACAATAAAGACACATTAATAAA AGAACAAACAGAGTACAGGAAAGCCATCCACAAGAAGTTCGCAAACGATGACAGA TTCAAAAATATGTTCAGTGCGAAGCTAATATCCGACATCTTACCAGAGTTTGTAATA CACAATAACAATTACAGCGCGAGCGAAAAGGAAGAGAAAACGCAAGTAATTAAGC TTTTTAGTAGGTTCGCTACCTCTTTCAAAGATTACTTCAAAAATCGTGCTAACTGCTT CTCAGCCGACGACATATCTTCAAGTTCCTGTCACCGTATCGTGAATGATAACGCTGA GATATTCTTCTCAAACGCCCTTGTATACCGTAGGATCGTAAAGTCCTTATCTAACGAT GATATAAACAAGATCAGTGGAGACATGAAAGACAGCCTTAAAGAGATGTCTCTAGA AGAAATTTACTCCTATGAAAAGTATGGGGAGTTTATAACACAGGAGGGGATCAGCT TCTACAACGACATCTGCGGAAAGGTGAACAGTTTCATGAATCTTTACTGCCAGAAGA ATAAAGAGAACAAAAATCTTTATAAGCTTCAAAAGTTGCACAAACAAATACTGTGC ATTGCCGATACATCATATGAGGTCCCCTATAAGTTCGAATCTGATGAGGAAGTTTAT CAATCTGTTAACGGCTTTCTAGACAATATCAGCTCAAAACACATCGTAGAAAGACTG AGGAAAATAGGTGATAATTATAATGGATACAACTTGGATAAAATATATATAGTCTCT AAATTTTACGAGTCAGTATCCCAGAAAACGTATAGGGATTGGGAGACCATCAACAC GGCGTTAGAGATTCATTACAATAACATCTTACCGGGAAACGGAAAAAGTAAGGCGG ACAAAGTAAAGAAAGCCGTTAAAAATGACTTACAAAAGAGTATAACAGAAATAAA CGAACTAGTAAGCAACTACAAGCTTTGTTCCGATGATAATATCAAGGCCGAGACAT ATATCCATGAGATCTCCCACATTCTAAACAATTTCGAAGCGCAAGAACTTAAATATA ATCCCGAAATCCACCTGGTGGAAAGTGAACTAAAGGCTAGTGAGTTAAAGAACGTT CTTGATGTTATCATGAACGCCTTCCATTGGTGCTCTGTTTTTATGACCGAGGAGTTGG TTGATAAAGATAATAATTTCTACGCTGAATTAGAGGAGATATACGACGAAATCTACC CAGTGATTTCACTATACAACTTGGTCAGGAACTATGTTACACAAAAGCCGTACAGCA CTAAGAAAATTAAGCTAAATTTCGGTATCCCCACGTTAGCCGACGGGTGGAGCAAG TCCAAAGAATATTCCAACAATGCGATTATTTTAATGCGTGACAATCTTTATTACCTTG GCATCTTCAATGCCAAAAACAAACCTGACAAAAAGATTATAGAAGGTAATACGTCC GAGAACAAAGGCGATTACAAGAAGATGATTTATAACCTACTGCCCGGACCAAACAA AATGATCCCCAAAGTTTTTCTTAGTTCTAAAACCGGCGTAGAGACGTATAAACCTTC TGCCTATATCTTAGAGGGATATAAGCAGAACAAACATATCAAATCTTCCAAGGACTT TGATATTACATTCTGCCACGATTTAATTGACTACTTCAAAAATTGCATAGCGATACA TCCGGAGTGGAAGAACTTTGGCTTCGACTTCAGTGATACATCCACCTATGAGGATAT ATCAGGCTTCTATCGTGAGGTCGAATTGCAAGGGTACAAAATCGATTGGACGTATAT ATCCGAGAAAGACATAGACCTTCTTCAAGAAAAGGGGCAGTTATATTTATTCCAAAT ATACAACAAGGACTTCAGTAAGAAGTCAACAGGTAATGACAACTTACACACCATGT ACTTGAAAAATTTATTTTCTGAAGAAAACCTAAAGGACATTGTACTAAAACTGAACG GGGAGGCAGAAATTTTTTTTAGAAAGAGCAGCATAAAAAACCCAATAATTCATAAG AAAGGAAGCATTTTAGTTAATAGGACGTACGAGGCAGAGGAAAAGGACCAGTTTGG CAATATCCAGATCGTAAGGAAAAATATTCCTGAAAACATATATCAGGAACTATATA AATACTTTAACGACAAATCCGACAAAGAATTATCCGACGAGGCTGCAAAGCTGAAG AACGTCGTAGGGCACCATGAGGCAGCGACTAATATTGTGAAAGACTATAGGTATAC ATACGACAAATACTTTCTGCACATGCCCATCACGATTAACTTCAAGGCGAACAAGAC GGGATTCATTAACGACCGTATATTACAATATATTGCTAAGGAGAAAGATCTGCATGT AATAGGTATCGACAGAGGCGAACGTAATTTAATCTACGTGTCCGTCATCGACACGTG CGGGAACATCGTAGAGCAAAAGAGTTTTAATATAGTAAATGGCTATGATTACCAAA TTAAGCTAAAGCAGCAAGAAGGAGCAAGACAGATAGCTAGGAAAGAATGGAAGGA GATAGGAAAAATAAAGGAGATCAAGGAGGGGTATCTTAGCCTAGTAATTCATGAAA TATCTAAGATGGTTATCAAATACAACGCTATCATAGCGATGGAAGACTTATCTTATG GTTTCAAGAAAGGAAGGTTCAAAGTAGAGCGTCAAGTTTATCAAAAGTTCGAAACG ATGTTGATTAATAAACTAAACTATTTGGTATTTAAAGATATATCTATCACCGAGAAT GGTGGTCTACTAAAGGGTTACCAGCTTACATACATACCGGACAAACTTAAAAACGTC GGACATCAGTGTGGATGCATTTTCTACGTTCCAGCTGCATATACCAGCAAGATCGAC CCAACGACTGGGTTCGTAAATATTTTTAAATTCAAGGATTTGACTGTCGACGCCAAA AGAGAGTTCATAAAAAAGTTCGATTCAATTAGGTACGACAGCGAAAAGAATTTGTT CTGCTTTACTTTTGACTATAACAATTTCATTACTCAGAACACTGTAATGTCTAAGTCC TCTTGGTCAGTCTATACTTATGGCGTTCGTATCAAACGTAGATTTGTTAACGGTAGAT TCTCAAATGAAAGTGATACAATAGATATCACGAAAGATATGGAGAAAACATTAGAA ATGACAGACATAAACTGGAGAGACGGACATGACTTGAGACAGGACATTATTGACTA CGAGATCGTGCAGCACATCTTTGAGATCTTTCGTTTGACCGTACAAATGCGTAACAG TTTATCTGAGCTTGAGGACAGGGACTACGATAGATTGATATCACCTGTATTAAATGA GAATAACATCTTCTATGATTCCGCAAAAGCAGGCGACGCTCTACCCAAAGACGCTG ATGCGAACGGTGCTTATTGCATAGCTTTAAAGGGTTTGTATGAGATCAAACAGATAA CAGAAAATTGGAAGGAAGATGGTAAGTTCTCCCGTGACAAGCTTAAAATATCAAAT AAGGACTGGTTCGATTTTATACAGAATAAGCGTTATTAAAACGTCCGGCAGCGACCA AAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCC GAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCT AA SEQ ID NO: 97 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAATGGAACTA ATAACTTCCAGAATTTCATTGGTATCTCCTCTTTACAAAAAACTCTAAGAAACGCCC TAATTCCGACTGAAACTACACAGCAATTCATCGTCAAAAACGGGATCATTAAGGAG GATGAGTTGAGGGGTGAAAATCGTCAAATTCTTAAAGACATCATGGACGACTACTA CAGGGGGTTCATCAGCGAGACGTTATCTAGTATAGACGATATAGACTGGACTTCACT GTTCGAGAAGATGGAAATCCAATTAAAAAATGGGGACAATAAAGATACACTTATAA AGGAACAGACAGAGTATAGAAAGGCAATACACAAAAAGTTTGCCAACGACGATCGT TTCAAGAACATGTTTAGTGCTAAATTGATTTCAGATATTCTGCCGGAATTTGTTATTC ACAACAATAATTATAGCGCCAGTGAGAAAGAAGAAAAAACGCAGGTTATCAAACTG TTCAGTCGTTTCGCTACATCTTTTAAGGATTACTTTAAAAACCGTGCAAATTGTTTTT CAGCCGACGATATTAGTAGCAGCTCTTGTCACCGTATTGTTAATGATAATGCGGAGA TTTTCTTTTCAAACGCATTGGTCTACAGGAGGATAGTCAAGTCCCTTTCAAATGACG ACATTAATAAGATCTCAGGTGACATGAAAGATTCCTTAAAGGAAATGTCCCTGGAA GAGATCTATTCCTATGAAAAGTACGGTGAGTTCATTACTCAAGAGGGTATAAGCTTT TACAATGACATATGTGGTAAGGTTAATAGCTTTATGAACCTGTATTGCCAGAAGAAC AAAGAAAATAAGAATCTGTATAAGTTGCAAAAGCTACACAAACAAATTTTGTGCAT TGCCGATACATCATACGAGGTGCCATACAAATTCGAGAGCGATGAGGAGGTTTATC AGAGCGTGAATGGATTCCTGGACAATATTAGTAGTAAGCATATCGTGGAAAGGCTT AGAAAGATAGGTGACAATTACAATGGCTACAATCTGGATAAAATCTACATCGTCTC AAAATTCTATGAAAGTGTATCCCAGAAGACGTACCGTGATTGGGAAACTATCAACA CCGCTCTGGAGATACATTACAACAATATACTTCCCGGAAACGGCAAGTCAAAAGCC GACAAAGTCAAAAAAGCGGTCAAGAACGATTTACAAAAGTCTATCACTGAAATTAA TGAATTAGTTAGTAATTACAAACTGTGTAGTGATGATAATATTAAGGCAGAGACTTA CATACACGAAATTTCACACATTTTAAACAACTTCGAGGCACAGGAACTTAAATATAA TCCTGAAATTCACCTGGTTGAAAGTGAATTGAAAGCCAGCGAGCTAAAGAACGTTTT GGACGTAATCATGAACGCATTCCACTGGTGCTCTGTCTTTATGACAGAGGAACTAGT GGATAAGGACAATAATTTTTATGCGGAGCTGGAGGAAATATACGATGAGATATATC CCGTAATATCATTATATAATCTGGTAAGAAACTATGTGACTCAAAAGCCGTATAGCA CCAAGAAAATTAAACTTAATTTCGGCATACCCACTTTAGCGGACGGCTGGTCAAAAT CCAAAGAGTATAGTAATAATGCCATCATCCTGATGCGTGACAACCTGTACTATTTAG GTATATTTAACGCCAAAAATAAACCCGACAAAAAGATTATAGAGGGCAACACCTCA GAGAACAAAGGTGATTATAAGAAGATGATTTACAACCTTTTACCCGGTCCTAATAAG ATGATTCCCAAAGTCTTTCTATCTAGCAAAACTGGTGTTGAAACATACAAACCCTCA GCTTATATTTTAGAAGGGTATAAGCAGAATAAGCATATTAAAAGCTCCAAAGATTTC GATATTACCTTTTGCCATGACTTGATAGACTATTTCAAAAATTGTATTGCCATTCACC CTGAATGGAAAAACTTCGGATTTGACTTCTCTGACACATCCACCTACGAAGACATTT CAGGTTTTTACAGGGAAGTCGAGCTACAGGGTTATAAAATTGATTGGACATACATCA GCGAGAAAGATATTGACCTACTTCAAGAAAAAGGGCAGCTATACCTGTTCCAGATA TACAATAAAGACTTCAGTAAAAAAAGCACCGGGAACGATAATCTTCACACAATGTA CTTAAAAAATTTATTTAGTGAAGAGAATCTGAAGGATATAGTGCTGAAGTTAAACG GGGAGGCAGAGATATTTTTTAGAAAATCTAGTATTAAGAATCCGATCATCCACAAG AAGGGTTCTATCCTTGTTAATAGGACTTATGAGGCAGAAGAAAAAGACCAATTCGG CAACATACAAATTGTCCGTAAAAATATCCCTGAGAACATTTATCAGGAACTATACAA GTACTTCAATGATAAAAGCGACAAGGAGCTGAGCGACGAGGCTGCTAAGTTAAAGA ATGTGGTGGGCCACCATGAGGCAGCAACGAATATTGTGAAGGACTATCGTTATACCT ACGATAAATACTTTCTTCATATGCCGATCACCATTAATTTCAAGGCAAACAAAACTG GCTTCATTAACGATCGTATCTTACAATATATCGCAAAAGAGAAAGACCTTCACGTTA TCGGGATCGATAGAGGCGAGCGTAACCTAATTTATGTTTCTGTGATAGACACCTGTG GGAACATAGTCGAACAGAAATCATTTAATATTGTTAACGGCTACGATTATCAGATAA AGTTGAAGCAACAAGAGGGTGCACGTCAAATAGCAAGGAAAGAATGGAAAGAAAT AGGCAAGATTAAAGAAATAAAAGAAGGTTATTTATCCCTTGTAATACACGAAATTA GCAAAATGGTGATTAAATATAATGCGATCATTGCCATGGAGGATCTTTCTTACGGCT TCAAAAAGGGGAGATTCAAAGTCGAGAGGCAGGTGTATCAGAAGTTTGAGACCATG CTAATCAATAAACTAAATTATCTAGTATTCAAAGACATAAGCATCACCGAAAATGGC GGCTTGTTGAAGGGTTATCAATTGACCTACATCCCAGATAAACTAAAAAACGTAGG GCATCAATGCGGATGTATATTTTACGTTCCAGCCGCATACACTTCCAAAATCGATCC AACTACGGGTTTTGTGAACATCTTCAAATTCAAAGACTTGACTGTCGATGCTAAGAG GGAGTTTATCAAGAAATTTGACTCCATTAGATACGACAGTGAGAAGAATCTGTTCTG TTTTACCTTTGATTATAACAACTTTATAACTCAAAACACAGTCATGAGTAAGTCATCT TGGTCAGTGTATACGTATGGTGTGAGGATTAAAAGGAGGTTTGTTAACGGGAGATTT TCCAATGAAAGTGATACAATAGATATAACCAAGGACATGGAAAAGACTCTTGAAAT GACCGACATTAACTGGAGAGATGGCCACGACTTACGTCAAGATATAATCGATTACG AGATAGTGCAACATATCTTTGAGATATTTAGGCTTACTGTCCAAATGCGTAACTCAT TAAGTGAGTTGGAGGACAGGGATTACGATAGGCTAATAAGTCCTGTTCTTAACGAA AACAATATATTCTACGATTCAGCAAAGGCGGGAGACGCCCTGCCCAAGGACGCGGA TGCTAACGGCGCATACTGTATTGCCCTGAAAGGCTTGTACGAGATAAAACAGATCAC GGAGAACTGGAAAGAAGATGGAAAATTCAGTCGTGACAAGTTAAAAATTAGTAACA AAGACTGGTTCGACTTTATTCAGAACAAGAGATATCTGAAACGTCCGGCAGCGACC AAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCC CGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGG CTAA SEQ ID NO: 98 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAACGGAACCA ATAACTTTCAAAACTTTATAGGCATCTCCAGTCTACAGAAGACACTACGTAACGCTT TGATACCAACTGAGACCACGCAGCAGTTTATCGTCAAGAACGGTATTATAAAGGAA GACGAGCTAAGGGGGGAAAACCGTCAGATCTTAAAGGACATCATGGATGACTACTA CAGAGGCTTCATAAGTGAGACTTTGTCTAGTATAGACGACATCGACTGGACCAGTTT ATTTGAGAAGATGGAAATTCAGTTAAAGAACGGGGACAATAAAGACACACTAATTA AAGAGCAGACCGAATACAGAAAAGCTATACACAAAAAGTTTGCCAACGATGATAGA TTCAAAAATATGTTTTCAGCAAAATTGATTTCCGACATATTGCCAGAATTCGTAATC CATAATAACAATTATTCTGCAAGTGAGAAGGAAGAGAAGACCCAAGTAATCAAGCT GTTTTCCCGTTTTGCTACGAGTTTCAAAGATTATTTCAAGAATAGGGCTAATTGTTTC TCCGCGGACGACATAAGTAGCAGTTCCTGTCACAGGATTGTGAACGATAATGCTGA GATATTTTTTTCCAATGCCCTAGTGTATAGGAGAATAGTTAAAAGCTTAAGCAACGA CGATATCAATAAAATTTCAGGGGACATGAAGGACAGCTTAAAGGAAATGAGTTTGG AGGAGATTTACAGTTATGAAAAATACGGAGAGTTTATAACTCAGGAAGGCATCTCTT TCTATAATGATATCTGTGGGAAGGTAAACTCCTTCATGAATTTATATTGCCAGAAGA ATAAGGAAAACAAAAATCTTTACAAGCTTCAAAAGTTACATAAGCAGATCTTATGT ATTGCCGACACGAGTTATGAAGTGCCTTATAAATTCGAGAGTGATGAGGAAGTGTAT CAGTCTGTTAACGGATTCCTAGATAATATAAGTTCCAAACATATAGTCGAGAGGCTG AGGAAGATTGGCGATAACTATAATGGATATAATCTTGACAAAATCTATATAGTCTCT AAATTTTATGAAAGCGTCAGCCAGAAGACATATAGAGATTGGGAAACTATAAACAC AGCCCTTGAAATACATTACAATAACATCCTACCCGGCAATGGTAAGTCTAAGGCAG ACAAAGTTAAAAAAGCAGTAAAGAATGACTTACAGAAGTCAATCACGGAGATAAAT GAGTTGGTCAGTAACTACAAATTATGCTCCGACGATAATATTAAGGCCGAAACATAT ATACACGAGATAAGTCATATATTAAACAATTTCGAAGCCCAGGAGTTAAAATATAA CCCTGAAATTCATCTGGTCGAAAGTGAGTTAAAGGCCAGTGAGTTAAAGAATGTACT TGACGTAATTATGAATGCTTTTCATTGGTGCTCCGTGTTCATGACCGAGGAGTTAGT AGATAAAGACAATAACTTTTACGCCGAACTTGAAGAGATATACGACGAGATTTATC CGGTAATCAGCTTGTACAACTTAGTTAGAAATTATGTAACACAGAAGCCTTACTCTA CTAAAAAAATAAAACTGAACTTTGGTATCCCAACTCTTGCAGATGGTTGGAGTAAAA GCAAGGAATATAGCAACAATGCGATCATCTTGATGAGAGACAACTTGTACTATTTGG GAATCTTCAACGCGAAAAATAAACCCGACAAAAAAATCATCGAAGGGAATACCTCT GAGAATAAAGGTGACTATAAGAAAATGATTTACAATCTACTTCCTGGTCCTAATAAA ATGATCCCGAAAGTGTTTCTTAGTTCTAAGACTGGTGTCGAGACGTACAAACCTAGC GCGTACATCTTAGAAGGGTACAAGCAGAATAAACACATCAAATCAAGCAAAGACTT CGATATTACTTTTTGCCATGACTTGATAGACTACTTTAAAAACTGCATAGCAATCCA CCCGGAGTGGAAAAACTTTGGCTTTGATTTCTCTGACACCTCTACATATGAGGACAT ATCTGGTTTTTACCGTGAGGTTGAATTGCAGGGATACAAAATTGACTGGACTTACAT ATCTGAAAAAGATATCGATCTATTGCAGGAGAAAGGCCAGCTTTACCTTTTCCAGAT CTATAATAAGGACTTCTCTAAGAAGTCTACAGGGAATGATAATTTGCACACTATGTA CTTAAAAAATCTGTTTTCCGAGGAAAACTTGAAAGACATTGTTTTAAAGTTGAACGG AGAAGCTGAAATATTTTTCAGAAAGAGCTCCATAAAAAACCCGATCATTCATAAGA AGGGATCTATCCTGGTTAACAGAACGTACGAAGCGGAAGAAAAAGACCAATTCGGA AACATTCAAATTGTTAGAAAGAATATCCCTGAGAACATCTACCAGGAGTTATATAAG TATTTTAATGATAAGTCAGATAAGGAACTATCTGACGAAGCGGCGAAGCTTAAAAA TGTTGTAGGACACCATGAGGCTGCTACAAATATAGTCAAGGACTACCGTTATACCTA CGATAAGTACTTTCTACACATGCCCATTACCATCAATTTTAAAGCTAATAAAACGGG TTTTATCAACGATCGTATCCTACAATATATTGCGAAAGAGAAGGATTTGCATGTCAT TGGCATTGATAGAGGTGAGAGGAACCTAATATACGTATCCGTGATTGATACGTGCG GGAACATAGTTGAACAGAAATCATTTAATATAGTTAATGGGTACGACTATCAGATTA AGCTAAAGCAACAAGAAGGCGCCAGGCAAATTGCCCGTAAAGAATGGAAAGAGAT CGGGAAGATCAAGGAAATAAAAGAAGGATACCTTTCCCTGGTCATCCATGAAATTA GCAAAATGGTGATTAAGTACAATGCCATAATCGCGATGGAGGACTTAAGCTACGGG TTCAAAAAGGGGAGGTTTAAGGTGGAGAGGCAAGTGTACCAGAAATTTGAGACCAT GCTAATCAACAAACTGAACTACCTAGTTTTTAAGGACATTTCAATTACAGAGAATGG AGGACTTTTAAAGGGTTACCAACTAACGTATATACCAGATAAGTTGAAAAATGTCG GTCACCAGTGTGGCTGCATCTTTTACGTTCCCGCCGCTTATACATCTAAAATTGATCC AACCACAGGCTTTGTAAATATCTTTAAATTCAAAGATTTAACTGTGGATGCAAAAAG AGAGTTTATCAAGAAATTCGATAGCATTCGTTATGATAGCGAGAAGAACCTGTTCTG CTTTACTTTCGACTATAACAACTTTATAACTCAAAACACCGTGATGTCAAAAAGCTC ATGGTCAGTCTACACCTATGGTGTAAGGATTAAAAGGCGTTTCGTGAATGGGAGATT CTCCAATGAAAGTGACACGATCGACATAACAAAGGACATGGAGAAGACACTAGAG ATGACTGATATTAATTGGAGAGACGGACACGATCTGCGTCAAGATATAATTGATTAT GAGATAGTACAGCACATATTTGAGATCTTCCGTTTGACTGTCCAAATGCGTAATTCC CTTTCTGAGCTGGAAGATAGGGACTATGATAGATTAATATCCCCTGTACTAAATGAG AACAACATTTTCTATGATAGTGCAAAAGCCGGGGATGCATTGCCGAAAGACGCTGA CGCTAATGGGGCGTACTGTATAGCTTTAAAGGGGCTTTACGAAATAAAGCAGATAA CCGAAAACTGGAAGGAAGATGGCAAATTCTCAAGGGACAAACTTAAGATCTCTAAC AAGGATTGGTTCGATTTTATACAAAACAAACGTTATTTGAAACGTCCGGCAGCGACC AAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCC CGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGG CTAA SEQ ID NO: 99 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAATAATGGTACAAA CAACTTTCAGAATTTCATTGGGATCTCTAGCTTACAGAAGACCCTGAGGAATGCGTT GATTCCAACTGAAACAACCCAGCAATTCATCGTGAAAAATGGGATAATCAAAGAGG ATGAGTTAAGGGGTGAAAACCGTCAAATATTGAAGGATATTATGGACGACTACTAC CGTGGATTCATCTCAGAGACGTTGAGCAGCATTGACGACATAGACTGGACTAGCCTT TTCGAGAAGATGGAAATTCAGTTAAAGAACGGAGATAACAAAGATACACTAATCAA GGAACAGACAGAATACAGAAAAGCAATTCATAAGAAATTCGCTAATGACGATCGTT TTAAAAACATGTTCTCTGCAAAATTAATTAGCGACATTCTGCCGGAATTCGTTATAC ATAATAATAACTACAGTGCTTCTGAAAAGGAAGAGAAAACTCAGGTAATAAAACTG TTCTCTCGTTTTGCCACATCCTTCAAAGACTACTTTAAAAATAGAGCGAACTGCTTTA GCGCCGACGATATTAGTTCTTCCTCATGCCACAGGATTGTCAACGATAATGCAGAGA TATTCTTTTCTAACGCACTAGTCTACAGAAGGATTGTAAAGTCTTTGTCAAATGATG ACATAAACAAGATTAGTGGAGATATGAAAGACTCTCTAAAGGAAATGAGCCTTGAG GAGATATACTCTTATGAAAAGTACGGTGAGTTTATTACCCAAGAAGGCATTAGTTTC TATAATGACATTTGTGGAAAAGTTAACAGTTTTATGAATCTATACTGTCAAAAAAAT AAGGAGAATAAAAATCTTTATAAGTTGCAAAAACTGCATAAGCAGATATTATGTAT AGCAGACACGAGCTATGAGGTACCGTACAAGTTCGAGAGCGATGAGGAAGTCTACC AATCTGTCAACGGATTTTTGGACAACATTTCTTCAAAACATATTGTGGAGAGGCTTA GGAAAATAGGCGACAATTATAATGGATATAACTTAGATAAGATATATATTGTTTCCA AATTCTACGAATCTGTAAGCCAGAAGACATACAGAGATTGGGAAACGATAAACACA GCCCTTGAAATTCACTATAACAACATACTACCTGGAAACGGCAAATCAAAGGCCGA CAAAGTTAAGAAGGCCGTAAAGAATGATTTACAGAAGAGCATAACGGAGATCAATG AGCTGGTGTCTAACTATAAATTGTGTAGCGATGACAACATAAAAGCCGAGACTTAC ATTCACGAAATTTCACACATACTTAACAACTTTGAAGCTCAGGAATTAAAGTATAAT CCCGAAATACACCTTGTGGAGTCCGAACTAAAGGCTAGTGAGCTTAAGAACGTCCT AGACGTAATTATGAATGCCTTCCACTGGTGTAGTGTTTTTATGACCGAGGAACTTGT TGACAAAGATAATAATTTTTATGCAGAACTAGAAGAGATATACGATGAAATATACC CGGTGATCAGTTTGTACAATCTTGTCAGGAACTATGTGACACAAAAGCCCTATTCAA CAAAGAAAATAAAACTTAATTTCGGAATTCCTACGTTAGCTGATGGCTGGTCTAAAT CCAAGGAATACAGCAACAACGCTATAATTCTGATGAGAGATAACTTGTACTATCTAG GCATCTTCAATGCCAAAAATAAGCCTGATAAGAAGATTATAGAGGGCAACACTTCA GAGAACAAGGGCGACTACAAGAAAATGATCTATAACCTATTGCCTGGCCCAAACAA GATGATTCCGAAGGTCTTCCTATCATCCAAGACCGGCGTTGAGACATACAAGCCATC AGCGTATATTTTAGAGGGGTACAAACAAAACAAGCACATAAAGTCTAGTAAAGACT TCGATATAACATTTTGTCATGACTTAATTGACTACTTTAAGAATTGCATCGCTATACA CCCGGAATGGAAGAATTTCGGCTTCGACTTCTCTGATACATCTACCTACGAGGACAT TAGCGGGTTTTACCGTGAAGTCGAATTACAAGGGTATAAGATAGATTGGACGTACAT CTCTGAGAAAGACATAGACTTGCTTCAGGAAAAGGGCCAGTTGTATCTATTCCAAAT ATACAATAAGGATTTTTCCAAGAAATCTACGGGTAATGACAATCTTCACACAATGTA TCTTAAGAACCTTTTCTCAGAAGAGAACCTGAAGGACATTGTCTTAAAACTAAATGG CGAAGCTGAGATTTTTTTCAGGAAGTCTTCAATTAAGAACCCGATAATCCACAAGAA GGGGAGTATTCTTGTGAATAGAACTTACGAGGCCGAAGAAAAAGACCAATTTGGTA ACATCCAGATAGTCAGAAAGAACATTCCAGAGAACATCTACCAAGAGCTATACAAA TATTTCAACGACAAGTCCGATAAGGAACTGTCCGATGAGGCAGCCAAGTTGAAGAA TGTCGTGGGTCATCATGAAGCTGCTACTAACATTGTCAAGGACTATCGTTATACTTA CGACAAGTATTTCCTACACATGCCGATAACAATTAATTTCAAGGCTAACAAAACAGG CTTTATCAACGATCGTATCTTGCAGTACATAGCTAAGGAAAAGGATTTGCATGTGAT TGGCATTGATAGAGGGGAGCGTAACTTGATATATGTGTCTGTCATAGACACGTGTGG CAACATCGTCGAACAGAAATCATTCAACATAGTAAACGGCTACGATTACCAAATTA AGCTGAAACAGCAAGAGGGTGCACGTCAAATTGCGCGTAAAGAGTGGAAAGAAATT GGTAAAATCAAGGAAATTAAAGAAGGCTACTTGTCTCTTGTTATACATGAAATTTCC AAGATGGTTATAAAGTATAACGCGATAATTGCTATGGAAGACTTATCATACGGGTTT AAAAAGGGGAGGTTCAAGGTAGAGAGGCAGGTCTATCAAAAGTTCGAGACGATGTT GATTAATAAACTAAACTATCTAGTGTTCAAAGATATCAGCATTACGGAGAACGGGG GGCTACTGAAAGGATATCAACTAACGTACATTCCCGATAAGTTAAAGAACGTTGGTC ATCAATGTGGTTGCATCTTCTACGTGCCTGCTGCCTATACGTCCAAAATAGATCCAA CTACTGGATTTGTTAACATCTTTAAATTCAAAGATTTAACCGTAGACGCCAAAAGGG AATTTATAAAAAAATTTGACAGCATCCGTTACGATAGCGAAAAGAATCTGTTCTGTT TTACTTTCGACTACAATAATTTCATCACGCAAAATACGGTAATGTCTAAGTCAAGTT GGAGCGTCTACACGTATGGAGTCAGGATCAAGAGGCGTTTCGTAAATGGAAGATTC TCTAATGAGTCAGATACTATAGACATCACGAAAGATATGGAGAAAACCTTGGAGAT GACGGATATTAACTGGCGTGATGGACACGATTTAAGACAGGACATTATTGACTATG AGATTGTGCAACACATCTTCGAAATATTCCGTCTAACAGTCCAAATGAGGAATAGCC TAAGTGAATTGGAGGACCGTGATTACGATAGGCTTATAAGTCCTGTCCTTAACGAAA ACAATATTTTCTATGATAGTGCTAAGGCGGGGGACGCACTGCCTAAAGACGCAGAT GCTAACGGGGCATACTGCATTGCGTTAAAGGGTCTGTACGAAATCAAGCAGATTAC GGAAAACTGGAAAGAGGATGGCAAGTTTAGCAGAGATAAGTTGAAGATAAGTAAC AAAGATTGGTTTGACTTTATTCAGAATAAAAGGTATTTAAAACGTCCGGCAGCGACC AAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCC CGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGG CTAA SEQ ID NO: 100 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAATAACGGCACTAA TAATTTCCAGAATTTCATCGGCATTAGCAGCTTACAAAAGACGTTGAGGAATGCCTT AATACCCACAGAAACTACTCAACAATTTATAGTGAAGAATGGGATAATTAAGGAAG ACGAGTTGAGAGGTGAAAATAGGCAAATCTTGAAAGACATTATGGATGACTACTAC AGGGGCTTCATTAGTGAAACGTTGTCTTCAATAGATGACATTGATTGGACTTCTTTGT TTGAGAAGATGGAAATACAGTTAAAGAACGGCGACAATAAGGATACACTTATCAAA GAGCAAACAGAATATAGAAAAGCAATTCACAAAAAGTTTGCTAACGATGATAGGTT CAAGAACATGTTTAGCGCTAAACTAATATCAGACATCCTTCCCGAGTTCGTTATTCA TAACAATAACTATAGTGCAAGTGAAAAAGAGGAGAAGACACAGGTGATTAAGCTGT TCTCCAGATTCGCGACTTCTTTCAAAGATTACTTCAAAAACAGAGCCAACTGTTTTTC AGCTGACGATATCTCTAGTAGTAGTTGTCACCGTATAGTGAACGATAACGCTGAGAT CTTCTTTAGCAATGCATTAGTGTATAGAAGGATAGTTAAGTCTCTAAGCAATGATGA TATCAATAAAATTTCCGGAGACATGAAGGACTCCCTAAAGGAAATGTCCTTAGAAG AGATCTACTCATATGAGAAATACGGGGAATTTATTACGCAGGAAGGGATCTCCTTTT ACAATGACATATGCGGGAAGGTCAACTCTTTCATGAACTTATACTGCCAAAAGAAC AAGGAGAACAAGAATTTATATAAACTTCAGAAACTTCACAAACAAATACTGTGCAT AGCCGATACCTCATATGAGGTTCCTTACAAATTTGAATCAGATGAAGAGGTATACCA ATCCGTTAACGGCTTTCTTGACAATATTAGCTCAAAGCACATCGTGGAGAGGTTGAG AAAGATTGGTGATAATTATAATGGCTACAATCTAGATAAGATATATATTGTTAGCAA GTTCTACGAGTCTGTGTCCCAAAAAACATATAGGGATTGGGAGACAATTAATACTGC TCTAGAAATCCATTACAACAACATCCTTCCTGGAAATGGCAAGAGTAAGGCCGACA AAGTCAAGAAAGCAGTGAAAAATGATCTGCAAAAATCAATTACTGAGATAAACGAG CTAGTATCTAATTACAAGCTTTGTAGCGACGATAACATTAAGGCAGAAACGTACATA CACGAGATTAGTCACATCTTAAATAATTTTGAAGCCCAAGAACTGAAATATAACCCT GAGATACACCTTGTTGAATCCGAGTTAAAGGCGTCTGAACTAAAAAACGTGTTAGA CGTTATTATGAATGCCTTCCACTGGTGTAGCGTCTTTATGACTGAGGAGTTGGTTGAT AAGGATAATAACTTTTACGCTGAATTGGAAGAAATTTATGACGAAATCTATCCTGTT ATTTCTCTATATAATTTGGTGAGAAATTACGTAACGCAAAAGCCCTATAGTACGAAA AAAATAAAACTAAATTTCGGGATCCCTACCCTAGCCGACGGTTGGTCTAAATCCAAG GAGTACTCAAACAATGCAATAATATTGATGAGGGACAACCTGTACTACCTAGGCAT ATTTAATGCCAAAAATAAGCCCGATAAAAAGATTATAGAAGGGAACACGTCAGAAA ATAAAGGAGACTATAAGAAAATGATCTACAACCTTTTGCCCGGCCCCAATAAAATG ATCCCGAAGGTCTTCCTAAGTAGCAAGACTGGCGTAGAGACCTACAAACCATCTGC ATACATTTTGGAGGGGTACAAGCAAAACAAGCACATAAAGAGTAGTAAGGATTTTG ACATTACATTCTGCCATGACTTAATTGACTACTTTAAAAATTGCATCGCAATTCACCC TGAATGGAAAAATTTTGGATTTGATTTCTCTGATACTTCAACATATGAGGATATTTCA GGGTTCTACAGGGAGGTCGAACTACAGGGTTACAAAATAGACTGGACGTATATTTCT GAGAAAGATATAGATTTGCTTCAGGAAAAGGGTCAGCTATATCTGTTCCAGATATAT AATAAGGACTTCTCCAAAAAGAGTACCGGAAATGATAATCTGCACACAATGTACTT AAAAAACTTGTTCTCTGAGGAGAATCTAAAAGACATCGTACTAAAACTTAACGGGG AGGCCGAAATTTTTTTTAGGAAGTCCAGCATCAAGAACCCGATTATTCATAAAAAAG GTAGCATTTTGGTGAACCGTACTTATGAGGCGGAAGAAAAAGACCAATTCGGTAAT ATTCAAATCGTTAGAAAGAACATCCCTGAGAACATTTATCAGGAACTATACAAATAC TTTAACGACAAATCAGATAAGGAGCTTTCTGATGAGGCAGCTAAATTGAAAAATGT AGTGGGACATCACGAAGCAGCCACTAACATAGTGAAGGACTACAGATACACATACG ATAAGTACTTCCTGCACATGCCTATTACAATTAACTTTAAAGCAAATAAAACAGGGT TTATTAACGACAGAATCTTACAGTATATTGCCAAAGAAAAGGATCTGCATGTGATAG GAATAGACAGAGGAGAAAGAAACCTGATATACGTCTCCGTGATTGATACATGTGGG AACATAGTAGAACAGAAGTCCTTTAACATTGTTAATGGGTACGATTATCAAATTAAA TTAAAACAACAAGAAGGAGCACGTCAAATAGCTAGGAAAGAATGGAAAGAGATAG GAAAAATTAAGGAAATTAAGGAGGGTTACCTGTCCCTTGTAATTCATGAAATATCCA AAATGGTAATTAAATATAACGCGATCATCGCGATGGAAGATCTAAGCTACGGGTTC AAAAAAGGCAGGTTTAAGGTGGAGAGGCAAGTTTACCAAAAGTTCGAGACAATGTT GATTAATAAGTTAAACTACTTAGTTTTCAAAGATATCTCCATAACCGAGAATGGCGG GCTTTTAAAAGGGTACCAACTAACATATATCCCGGATAAATTGAAGAACGTTGGAC ACCAGTGTGGCTGCATATTTTATGTACCCGCTGCGTATACTTCTAAAATTGACCCGA CCACCGGGTTTGTAAACATATTCAAGTTTAAGGACCTAACAGTTGACGCCAAACGTG AGTTCATCAAGAAGTTCGATAGTATAAGGTATGACTCTGAGAAGAACCTTTTCTGCT TCACGTTTGACTATAATAATTTCATCACCCAAAATACAGTTATGTCAAAAAGCTCTT GGTCAGTATATACGTATGGCGTAAGGATTAAGCGTAGGTTCGTGAACGGTAGATTTT CCAACGAGTCAGATACTATTGATATTACCAAGGATATGGAGAAGACATTAGAAATG ACAGATATAAATTGGAGGGATGGGCACGATCTAAGGCAAGATATCATTGATTACGA AATTGTTCAGCACATATTCGAGATATTCCGTCTTACAGTACAAATGCGTAACAGCTT GTCTGAGTTGGAAGATCGTGACTATGACAGGTTGATATCACCGGTCTTGAACGAGAA CAATATATTCTACGACAGCGCTAAGGCGGGAGACGCTCTGCCTAAAGACGCAGATG CCAATGGGGCGTACTGCATTGCCTTAAAAGGCTTATACGAGATTAAACAGATCACA GAGAACTGGAAAGAGGACGGCAAGTTTTCTAGAGATAAATTGAAAATCTCAAACAA AGACTGGTTCGATTTCATCCAAAACAAAAGATACCTTAAACGTCCGGCAGCGACCA AAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCC GAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCT AA SEQ ID NO: 101 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAATGGAACTA ACAACTTCCAGAACTTTATCGGCATCTCTTCCCTCCAAAAGACACTGAGAAATGCAC TGATCCCAACCGAAACGACTCAACAATTTATTGTTAAGAACGGCATCATAAAAGAA GACGAGCTTCGCGGCGAGAACCGCCAGATACTTAAGGATATTATGGACGATTATTA CCGAGGCTTTATCAGCGAAACTCTTAGCTCTATTGATGATATCGACTGGACCTCCCT CTTCGAAAAAATGGAGATACAGCTCAAGAACGGCGATAATAAAGACACCTTGATAA AGGAACAGACTGAGTACAGGAAAGCGATCCACAAGAAATTCGCGAACGACGACAG GTTTAAAAACATGTTCTCTGCAAAATTGATATCCGACATCTTGCCGGAATTTGTGAT ACACAACAATAACTATAGCGCTTCAGAGAAAGAAGAGAAGACCCAAGTAATCAAGT TGTTCAGCCGCTTCGCAACGTCTTTTAAAGATTACTTTAAGAACCGGGCCAATTGTTT CTCCGCGGATGATATTAGCTCATCAAGTTGCCATCGAATTGTCAATGATAATGCGGA GATCTTCTTCAGCAATGCGCTGGTCTACAGACGAATCGTAAAAAGTCTTTCAAATGA CGACATCAATAAGATTAGTGGAGATATGAAGGATTCCCTTAAGGAAATGAGTCTTG AAGAAATATACTCATACGAAAAGTACGGGGAATTTATTACCCAGGAGGGGATCTCC TTCTATAACGACATCTGTGGAAAAGTAAACTCATTCATGAACCTGTACTGTCAGAAA AACAAAGAAAACAAAAATCTGTATAAACTCCAAAAATTGCACAAGCAAATATTGTG TATAGCGGACACATCATACGAGGTTCCATATAAGTTCGAAAGTGATGAAGAAGTCT ACCAATCAGTGAATGGGTTTCTGGACAACATTAGTTCCAAGCACATAGTTGAACGAC TGCGAAAGATTGGTGACAATTACAACGGCTATAATTTGGACAAGATTTATATAGTTA GCAAATTTTATGAATCCGTATCACAAAAGACTTATAGAGACTGGGAAACAATCAAC ACGGCACTTGAGATCCATTATAACAATATTCTTCCAGGGAACGGCAAAAGCAAGGC TGATAAGGTAAAAAAGGCCGTTAAGAATGATCTTCAAAAATCCATAACGGAGATCA ACGAACTTGTAAGTAACTACAAATTGTGCTCTGACGACAATATAAAGGCTGAAACG TATATTCACGAGATTAGCCATATCCTGAATAACTTTGAGGCCCAAGAACTCAAGTAT AACCCGGAAATACATTTGGTAGAAAGCGAGCTTAAAGCGAGTGAGCTGAAAAACGT CCTCGATGTGATCATGAATGCTTTCCACTGGTGTAGTGTCTTTATGACTGAGGAGTTG GTTGATAAAGACAATAATTTCTACGCTGAACTGGAAGAAATTTACGACGAAATCTAT CCAGTGATCTCCCTCTATAACCTCGTTCGAAACTACGTGACGCAGAAACCTTATTCT ACAAAGAAAATTAAGTTGAACTTCGGCATTCCTACACTTGCTGACGGATGGTCCAAA TCCAAAGAGTACTCAAACAACGCAATCATCCTCATGCGGGATAACCTTTATTATTTG GGCATTTTCAACGCCAAAAACAAACCTGATAAAAAGATAATTGAAGGCAATACGAG TGAGAACAAGGGCGACTACAAAAAAATGATATATAACTTGTTGCCAGGCCCCAACA AGATGATTCCTAAAGTTTTTCTGTCTTCTAAGACTGGAGTTGAAACTTACAAACCCTC CGCCTACATTCTTGAAGGGTATAAACAGAATAAGCACATAAAGTCCTCAAAGGATTT CGACATTACGTTTTGCCATGACCTCATCGACTATTTCAAGAACTGTATCGCCATACAT CCGGAGTGGAAGAATTTTGGATTTGATTTCTCCGACACATCTACCTATGAAGACATA AGCGGTTTCTACCGGGAGGTCGAGCTTCAGGGCTATAAGATAGATTGGACATACATT AGTGAAAAAGATATCGATCTTCTGCAAGAAAAGGGACAACTTTACCTTTTTCAGATT TATAATAAAGACTTTTCAAAAAAGTCCACAGGGAACGATAATCTGCACACCATGTAT CTCAAGAATCTGTTTAGTGAAGAAAACCTTAAAGACATAGTTTTGAAGCTTAACGGA GAGGCTGAGATTTTTTTTAGAAAGTCCTCAATTAAAAACCCTATAATACACAAGAAA GGCTCTATTCTTGTTAACAGGACATATGAAGCCGAGGAGAAAGATCAGTTTGGCAAT ATCCAGATTGTTCGCAAGAATATCCCGGAAAATATATATCAGGAGCTGTATAAATAC TTTAACGACAAGAGCGACAAGGAGCTGAGTGACGAGGCCGCGAAGCTTAAGAATGT AGTAGGTCACCACGAAGCAGCCACCAATATCGTCAAAGACTATAGGTACACGTACG ACAAGTACTTTTTGCACATGCCTATAACTATAAACTTCAAAGCTAATAAAACTGGGT TTATTAATGACAGGATTCTCCAATACATCGCTAAAGAGAAGGATCTGCATGTAATTG GCATAGACAGAGGTGAGAGAAACTTGATATATGTCAGCGTAATAGACACATGTGGC AATATCGTGGAACAGAAGTCTTTTAACATCGTCAATGGTTACGACTACCAAATTAAG TTGAAACAGCAGGAAGGCGCACGACAGATCGCACGAAAGGAATGGAAAGAGATAG GCAAAATAAAAGAAATAAAGGAGGGCTATCTCAGTCTCGTTATACACGAAATTTCA AAAATGGTTATTAAGTACAATGCAATCATAGCGATGGAGGATCTCAGTTATGGGTTC AAAAAGGGTCGGTTTAAAGTTGAGCGCCAAGTGTACCAAAAGTTCGAGACAATGCT GATTAACAAGCTGAACTACCTCGTCTTCAAAGATATAAGTATTACGGAGAACGGTG GCCTTCTTAAAGGCTATCAACTTACTTACATCCCGGACAAGCTCAAAAACGTAGGGC ACCAATGCGGGTGTATTTTCTATGTGCCTGCGGCATATACGTCAAAGATTGACCCAA CCACAGGATTCGTAAACATATTCAAGTTTAAGGACCTCACCGTTGATGCGAAAAGG GAGTTCATTAAAAAATTTGATTCTATTCGATATGATAGTGAGAAAAATCTCTTTTGTT TCACATTTGACTATAATAATTTTATTACTCAGAATACTGTCATGAGCAAGTCATCTTG GTCAGTGTACACATACGGGGTGCGGATCAAACGCAGGTTCGTCAATGGTCGCTTCTC AAACGAATCAGACACCATTGACATCACAAAGGACATGGAAAAAACCCTTGAGATGA CCGACATTAATTGGCGCGATGGTCATGATCTGCGGCAAGACATCATAGACTACGAA ATCGTCCAACACATCTTTGAGATCTTTCGCTTGACGGTCCAAATGCGGAACTCCCTG TCCGAGCTCGAGGATAGAGATTATGATCGGCTGATATCTCCCGTGCTTAATGAAAAT AACATCTTCTACGACTCCGCCAAGGCGGGTGATGCCCTGCCGAAGGATGCGGATGCT AATGGCGCTTATTGCATTGCTCTTAAGGGGCTCTATGAGATAAAGCAGATCACGGAA AACTGGAAAGAAGACGGTAAGTTTAGTAGAGACAAGCTGAAGATCTCAAATAAAGA CTGGTTTGATTTCATACAGAACAAGCGGTACCTGAAACGTCCGGCAGCGACCAAAA AAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAA AAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 102 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAACAATGGCACTAA CAATTTTCAGAATTTCATCGGCATTTCAAGTCTGCAAAAAACTCTGAGGAATGCTTT GATCCCTACTGAAACCACTCAGCAATTTATAGTCAAGAACGGTATAATTAAAGAAG ATGAACTCAGGGGTGAAAATAGACAAATACTCAAGGACATTATGGATGACTATTAT AGAGGCTTCATCTCAGAGACTCTCTCATCAATAGATGATATCGATTGGACTAGCCTT TTCGAGAAAATGGAGATTCAGTTGAAAAATGGTGATAACAAAGATACGTTGATAAA GGAACAGACCGAGTACAGGAAAGCCATTCATAAGAAATTTGCTAATGACGATAGAT TTAAGAATATGTTTAGTGCAAAACTGATTAGTGACATTCTGCCGGAGTTCGTTATCC ATAATAATAACTACTCTGCATCCGAAAAGGAGGAAAAGACGCAAGTTATTAAACTG TTCAGCCGCTTCGCCACAAGCTTCAAGGACTACTTCAAAAATAGAGCCAACTGCTTT TCTGCCGACGATATATCATCATCTTCATGCCATCGGATCGTTAACGATAACGCCGAG ATATTCTTCAGCAACGCCCTTGTATATCGAAGAATAGTCAAAAGTCTGAGTAATGAT GATATTAATAAAATTAGCGGTGATATGAAAGACTCCCTGAAGGAAATGTCACTGGA GGAAATTTATAGTTACGAAAAGTACGGCGAATTCATTACTCAAGAAGGCATATCCTT CTATAACGACATTTGCGGAAAGGTCAACTCATTCATGAACCTTTATTGCCAGAAGAA TAAGGAGAATAAAAATCTTTACAAATTGCAAAAACTTCACAAACAAATTCTTTGCAT CGCGGATACGTCCTACGAAGTTCCTTACAAATTTGAATCCGATGAGGAAGTGTATCA GAGTGTCAATGGATTTTTGGATAATATCTCTTCAAAACATATTGTGGAGAGATTGCG CAAAATAGGTGATAACTACAATGGCTACAACCTGGACAAGATTTATATTGTTAGCAA GTTCTATGAAAGTGTCAGTCAAAAGACCTACAGAGATTGGGAGACAATCAACACGG CGCTCGAAATACACTACAATAACATCCTCCCCGGCAATGGGAAGAGTAAAGCCGAT AAGGTTAAAAAAGCTGTTAAGAACGACCTCCAGAAATCCATCACGGAAATAAACGA GCTGGTTTCCAACTATAAGCTGTGTAGCGATGATAATATTAAGGCTGAGACATATAT ACATGAGATCAGCCACATTCTCAACAATTTCGAGGCACAGGAACTCAAATACAATC CCGAGATTCACTTGGTGGAAAGTGAGTTGAAGGCGTCAGAGCTTAAGAATGTACTT GACGTAATAATGAATGCTTTTCATTGGTGCTCCGTGTTCATGACTGAGGAACTCGTG GATAAGGATAATAACTTTTATGCGGAGTTGGAAGAGATATACGATGAAATATACCC GGTTATCTCACTGTATAATCTGGTCAGAAATTACGTGACCCAAAAGCCTTATAGTAC AAAAAAAATAAAGTTGAACTTCGGTATTCCGACATTGGCAGATGGTTGGTCCAAAA GCAAAGAATACTCTAATAACGCCATTATATTGATGCGAGACAATTTGTATTACCTTG GGATCTTTAACGCGAAAAACAAACCGGATAAGAAGATCATCGAAGGTAATACATCT GAGAATAAGGGGGATTACAAGAAGATGATTTATAATCTGTTGCCGGGGCCAAACAA GATGATTCCGAAGGTCTTTCTGTCATCTAAGACAGGAGTAGAGACCTACAAACCTTC TGCGTACATTTTGGAAGGCTACAAACAGAACAAGCATATAAAATCTAGCAAGGACT TTGATATCACGTTTTGTCATGATCTGATAGATTATTTCAAAAACTGCATCGCTATACA TCCTGAGTGGAAGAATTTCGGCTTTGACTTTTCTGACACCAGCACATACGAAGACAT CTCAGGTTTCTACCGGGAAGTCGAGCTCCAGGGGTACAAGATTGACTGGACATATAT AAGTGAAAAAGACATCGACCTCCTCCAAGAGAAGGGCCAACTTTACCTGTTCCAGA TCTATAACAAAGACTTTTCTAAAAAGTCCACGGGTAACGACAACTTGCACACTATGT ATCTGAAAAACTTGTTCTCTGAAGAGAACCTCAAGGACATCGTCCTGAAGCTTAACG GGGAGGCGGAGATCTTCTTTAGAAAGTCCTCTATCAAAAATCCCATTATCCATAAAA AGGGCTCTATACTCGTTAATAGGACATATGAAGCGGAGGAAAAAGATCAATTTGGG AACATCCAGATCGTCCGGAAAAATATACCTGAGAATATCTATCAAGAGCTGTACAA GTATTTTAATGATAAGTCAGACAAAGAGCTCAGTGATGAGGCGGCAAAGCTCAAGA ACGTGGTGGGGCATCATGAAGCTGCGACGAACATTGTCAAAGATTATAGATACACT TACGATAAATACTTCCTCCACATGCCGATAACGATTAACTTCAAAGCCAATAAGACG GGGTTTATAAATGATCGGATCCTTCAGTACATTGCGAAAGAGAAAGACCTCCATGTG ATCGGAATTGACCGAGGAGAAAGGAATCTGATTTACGTGTCCGTGATTGATACTTGC GGGAATATAGTCGAGCAAAAGAGTTTCAACATAGTCAACGGGTATGACTATCAGAT AAAGCTCAAACAGCAGGAAGGTGCGAGGCAAATTGCGCGCAAAGAGTGGAAGGAG ATAGGCAAGATTAAAGAAATCAAGGAAGGTTATCTCAGCTTGGTGATCCATGAAAT ATCTAAGATGGTTATAAAGTACAATGCCATAATAGCCATGGAGGATCTTTCCTACGG GTTTAAGAAGGGCCGATTTAAAGTGGAGCGACAAGTTTACCAGAAGTTCGAAACCA TGTTGATTAACAAACTTAACTATTTGGTGTTCAAGGATATAAGTATAACCGAAAACG GCGGTTTGCTTAAGGGTTATCAGCTCACGTATATTCCTGATAAACTTAAAAACGTTG GACACCAGTGTGGATGTATCTTCTACGTGCCAGCCGCTTACACTAGTAAGATAGATC CTACCACGGGGTTTGTGAATATTTTTAAGTTTAAAGACTTGACAGTCGACGCCAAAA GGGAATTTATAAAAAAGTTTGATTCTATCCGCTACGATAGTGAAAAAAATCTCTTTT GCTTTACTTTCGACTATAACAACTTCATTACGCAGAACACTGTCATGAGTAAGTCCA GCTGGAGCGTCTACACATATGGCGTCCGAATTAAACGACGATTTGTAAACGGGCGG TTTTCAAACGAATCTGACACGATAGACATTACCAAGGATATGGAGAAGACACTTGA GATGACCGACATAAACTGGCGGGACGGTCACGATCTTCGGCAGGACATAATTGATT ACGAAATCGTCCAGCATATATTCGAAATATTTCGACTTACAGTGCAAATGCGGAACA GTCTCTCTGAACTGGAAGATCGCGATTATGACCGGTTGATTTCTCCGGTCCTCAATG AAAATAACATATTTTATGATAGTGCTAAGGCAGGTGATGCGTTGCCAAAGGATGCA GACGCTAATGGTGCCTATTGTATCGCGCTCAAGGGATTGTACGAGATAAAGCAAATT ACGGAGAACTGGAAGGAGGATGGTAAGTTTAGCCGAGACAAGTTGAAGATTAGCAA TAAAGACTGGTTTGATTTTATCCAAAACAAGAGGTACCTGAAACGTCCGGCAGCGA CCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAG CCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGG GCTAA SEQ ID NO: 103 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAATAACGGAACTA ATAACTTTCAAAATTTCATAGGTATTTCAAGCTTGCAGAAGACCCTGAGGAATGCCC TGATTCCAACCGAGACAACGCAGCAGTTCATAGTCAAAAATGGCATTATTAAGGAA GATGAGCTGCGGGGGGAAAACCGACAGATACTCAAGGATATTATGGACGACTATTA CCGGGGATTTATCTCAGAAACGCTGAGCAGTATTGATGACATCGATTGGACCAGTCT TTTCGAGAAAATGGAAATTCAACTTAAGAATGGTGACAATAAAGACACTCTCATAA AGGAGCAAACTGAATACCGAAAAGCCATACACAAAAAGTTTGCCAACGATGACCGC TTTAAAAACATGTTTTCAGCTAAGCTCATTAGCGACATTCTCCCCGAGTTTGTGATTC ATAACAATAACTATAGCGCATCCGAGAAGGAGGAAAAAACCCAAGTTATCAAATTG TTCAGTAGATTCGCTACGAGCTTTAAAGATTACTTTAAAAACCGGGCTAACTGCTTC AGTGCAGACGATATCAGCTCCTCATCCTGTCATCGCATCGTCAATGATAATGCTGAG ATCTTCTTTTCTAATGCACTGGTTTACCGCAGGATAGTTAAGTCTCTTAGTAACGACG ACATCAACAAGATATCAGGAGATATGAAGGATTCCCTTAAAGAAATGAGTCTCGAG GAGATATATTCTTATGAAAAATACGGCGAATTTATTACCCAAGAGGGCATTAGTTTC TATAATGACATATGCGGAAAAGTTAATAGTTTTATGAATCTCTATTGTCAGAAGAAT AAGGAGAATAAGAACCTCTACAAATTGCAGAAGTTGCACAAGCAAATTCTGTGTAT CGCGGACACCTCTTACGAGGTCCCATATAAGTTCGAGAGTGATGAAGAAGTATACC AGAGCGTTAATGGGTTCCTGGACAACATCTCAAGTAAACACATAGTCGAAAGGCTC CGAAAGATCGGTGATAACTATAACGGATATAATTTGGATAAAATTTATATAGTTAGC AAATTTTACGAGAGCGTCAGTCAGAAGACCTACCGGGACTGGGAGACCATAAACAC AGCGCTGGAAATACATTATAACAACATACTGCCTGGGAACGGTAAGTCAAAGGCAG ACAAGGTTAAAAAGGCTGTGAAGAATGACCTGCAAAAATCAATTACAGAAATAAAT GAGTTGGTAAGTAATTACAAACTTTGCAGCGATGATAATATAAAGGCAGAGACGTA CATACATGAAATATCTCATATCCTCAACAATTTCGAAGCCCAAGAACTGAAGTACAA CCCGGAAATTCATCTTGTAGAGTCTGAGTTGAAGGCCTCCGAATTGAAAAACGTTCT TGACGTAATTATGAATGCCTTCCACTGGTGCTCAGTATTCATGACGGAAGAGCTCGT GGATAAAGACAACAATTTTTACGCTGAACTGGAAGAAATATATGACGAGATTTACC CCGTAATTTCACTCTACAACTTGGTACGAAATTACGTTACCCAAAAGCCATACTCAA CAAAAAAAATTAAACTGAACTTCGGGATACCCACCCTCGCAGATGGATGGTCAAAG TCCAAAGAGTACAGTAACAATGCAATTATCCTGATGCGAGACAACCTTTATTACCTC GGGATTTTCAACGCTAAAAATAAACCTGATAAAAAAATAATTGAGGGTAATACCTC TGAAAACAAGGGGGATTATAAAAAGATGATATACAATCTGCTGCCTGGCCCGAACA AAATGATTCCTAAAGTCTTCTTGTCTTCCAAGACTGGAGTCGAAACCTACAAGCCAA GTGCTTATATACTCGAAGGGTACAAACAAAATAAGCACATAAAATCCAGCAAGGAT TTTGATATTACATTCTGCCACGATTTGATTGATTATTTTAAGAACTGTATAGCCATCC ACCCAGAATGGAAGAATTTTGGTTTTGATTTTAGCGATACCTCAACATATGAGGATA TCTCTGGCTTTTACCGCGAGGTAGAACTGCAAGGTTATAAGATCGATTGGACTTATA TTTCTGAAAAGGACATAGATCTCCTGCAAGAGAAAGGGCAACTTTATTTGTTTCAAA TATACAACAAAGATTTTAGTAAGAAGAGTACTGGCAATGATAACCTTCACACTATGT ATCTGAAGAACCTTTTTTCTGAGGAGAACTTGAAGGACATAGTCCTTAAACTCAATG GGGAAGCTGAAATATTCTTTCGCAAAAGCTCCATTAAAAACCCGATCATTCATAAAA AGGGTTCCATCTTGGTAAACCGCACATACGAGGCGGAAGAAAAAGATCAGTTCGGA AATATCCAGATCGTAAGGAAGAATATCCCCGAAAATATATACCAAGAGCTTTACAA ATATTTTAACGATAAGTCAGACAAGGAACTGTCAGACGAAGCAGCCAAGTTGAAGA ATGTCGTAGGGCACCACGAAGCAGCTACAAACATAGTTAAAGATTATCGGTACACC TACGATAAATATTTCCTGCATATGCCAATAACCATAAACTTCAAAGCCAACAAAACA GGGTTCATCAATGACCGAATACTTCAGTATATAGCCAAGGAAAAAGACCTGCATGTT ATAGGAATAGATAGAGGTGAGCGCAACTTGATATATGTCAGCGTGATAGACACCTG CGGAAATATCGTCGAGCAAAAAAGTTTCAACATTGTTAATGGCTACGATTACCAAAT TAAATTGAAGCAGCAAGAGGGGGCTCGGCAAATCGCGCGAAAGGAATGGAAAGAA ATCGGGAAGATTAAAGAAATTAAAGAGGGCTACCTGTCTCTTGTAATTCACGAAAT ATCTAAGATGGTCATCAAGTATAATGCCATTATTGCGATGGAAGATCTGTCCTACGG ATTTAAGAAAGGCAGGTTTAAAGTCGAAAGGCAGGTGTACCAGAAATTCGAGACCA TGCTGATTAATAAGCTCAACTATCTCGTATTTAAGGATATTTCTATAACTGAAAATG GAGGGCTTCTCAAAGGATATCAACTCACATACATACCTGATAAGCTGAAGAACGTA GGCCACCAGTGTGGATGCATATTCTATGTACCAGCTGCATACACAAGCAAGATCGAT CCAACTACTGGGTTTGTCAATATCTTCAAATTTAAGGACTTGACGGTCGATGCCAAA CGGGAGTTCATCAAAAAGTTTGATAGTATTCGATATGATAGTGAGAAGAACTTGTTT TGCTTCACATTTGACTACAACAATTTCATAACGCAAAATACGGTTATGTCTAAATCC TCATGGAGCGTCTACACTTACGGAGTGAGGATAAAGCGGCGCTTCGTAAATGGCAG GTTTAGCAATGAATCCGACACGATTGACATAACCAAGGATATGGAGAAAACCCTCG AGATGACCGATATAAATTGGCGGGATGGACACGATCTGCGACAAGACATAATCGAT TATGAAATCGTGCAGCACATATTTGAGATATTCAGGCTTACGGTCCAAATGAGAAAT TCCCTTTCCGAACTTGAAGACCGCGATTACGACCGACTGATAAGCCCCGTTCTGAAC GAAAATAACATCTTCTACGACAGCGCTAAAGCGGGAGACGCGCTGCCGAAAGATGC GGACGCAAATGGAGCCTATTGTATCGCCTTGAAAGGGTTGTACGAGATCAAACAGA TAACCGAGAATTGGAAGGAGGATGGGAAGTTTAGTCGAGACAAACTTAAAATAAGC AACAAGGACTGGTTCGACTTTATTCAAAACAAACGATATCTCAAACGTCCGGCAGC GACCAAAAAAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGC AGCCCGAAAAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCC GGGCTAA SEQ ID NO: 104 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAATAATGGTACTAA CAATTTTCAAAACTTTATCGGCATCTCTTCACTTCAGAAAACTCTTCGGAACGCCCTT ATACCGACGGAGACAACGCAGCAGTTTATAGTTAAAAACGGGATCATTAAAGAAGA TGAACTCAGAGGGGAAAACAGGCAAATATTGAAGGACATTATGGACGATTACTACC GGGGGTTTATTTCAGAGACCCTTTCATCTATTGATGACATAGATTGGACCTCCCTTTT CGAGAAAATGGAGATACAATTGAAAAACGGCGACAATAAAGATACACTTATCAAGG AACAAACTGAGTATCGCAAGGCGATTCACAAGAAGTTTGCGAATGACGATCGCTTT AAGAATATGTTTTCTGCGAAGCTCATAAGTGACATTCTGCCTGAATTTGTCATTCATA ACAACAATTATTCTGCTAGCGAAAAAGAGGAAAAAACTCAAGTCATTAAGCTTTTTA GCAGGTTCGCTACTAGTTTTAAAGACTATTTTAAGAACCGGGCGAATTGCTTTAGCG CTGACGACATATCATCCTCATCCTGTCATCGCATAGTCAATGATAATGCAGAAATAT TCTTTTCTAATGCGCTCGTGTATCGGAGAATAGTGAAAAGCCTCTCTAACGATGACA TTAACAAAATAAGCGGCGATATGAAGGATAGTCTGAAGGAAATGTCCCTCGAAGAA ATATACTCATACGAGAAGTACGGAGAATTTATCACCCAGGAAGGAATTAGTTTTTAC AACGACATCTGTGGTAAGGTTAACTCTTTTATGAATCTGTATTGTCAAAAGAATAAA GAAAATAAAAATCTTTATAAGCTCCAAAAGCTTCACAAACAAATCTTGTGCATTGCG GATACGTCATACGAAGTACCTTACAAATTTGAAAGCGACGAAGAGGTGTATCAGTC AGTGAATGGGTTCCTTGACAATATTTCTAGCAAACATATTGTGGAGCGACTTCGAAA GATCGGTGATAATTACAATGGCTATAATTTGGATAAAATTTACATAGTTAGTAAGTT TTATGAATCCGTCTCACAAAAGACGTACCGAGATTGGGAGACCATCAACACTGCTCT GGAGATTCATTACAATAATATATTGCCTGGGAATGGGAAGTCAAAGGCCGACAAGG TTAAAAAAGCCGTAAAAAACGATCTTCAAAAGTCCATTACCGAGATAAATGAACTT GTATCCAACTATAAGTTGTGCTCTGACGATAATATTAAAGCAGAAACGTATATCCAC GAAATAAGTCACATCCTGAACAACTTCGAAGCTCAAGAGCTCAAGTATAATCCTGA AATTCATCTCGTCGAAAGCGAGCTGAAAGCATCCGAGTTGAAGAATGTGCTTGATGT GATCATGAACGCATTCCATTGGTGCAGTGTGTTCATGACCGAAGAACTTGTAGACAA AGACAACAACTTCTACGCTGAATTGGAAGAGATTTACGATGAAATTTACCCCGTGAT ATCCCTCTATAATCTGGTAAGAAATTACGTCACGCAAAAACCATACAGTACCAAGA AAATAAAGCTCAACTTTGGTATTCCGACGTTGGCAGATGGGTGGAGTAAGAGCAAG GAGTATTCTAACAATGCAATCATCCTCATGCGCGACAATTTGTATTATCTGGGGATC TTCAACGCGAAAAATAAGCCCGACAAAAAGATAATAGAAGGCAATACGTCCGAGA ACAAAGGGGACTATAAGAAAATGATTTATAACCTTCTTCCAGGACCCAACAAGATG ATCCCAAAGGTTTTCTTGAGTTCAAAAACCGGCGTAGAAACTTATAAACCGTCCGCC TACATTCTGGAAGGGTACAAGCAAAACAAGCACATTAAGTCATCTAAGGATTTCGA CATTACTTTTTGTCATGATTTGATAGACTACTTCAAAAATTGTATAGCGATACATCCG GAATGGAAAAATTTTGGGTTCGATTTTTCCGACACAAGTACTTATGAAGACATCTCA GGGTTTTATAGGGAAGTTGAACTGCAAGGTTACAAAATAGACTGGACTTATATTAGT GAGAAGGACATTGATTTGCTCCAGGAAAAGGGTCAATTGTATCTGTTCCAGATATAT AACAAGGATTTCTCTAAAAAATCTACAGGTAACGACAATCTCCACACGATGTACCTC AAGAATCTCTTCAGCGAAGAGAATTTGAAGGATATCGTACTTAAGCTCAATGGAGA AGCGGAAATATTCTTCAGAAAGTCCAGCATTAAGAATCCTATAATTCACAAGAAAG GGTCAATTCTCGTAAACCGGACTTATGAGGCCGAAGAAAAAGATCAGTTTGGTAAC ATTCAGATTGTACGGAAAAACATTCCCGAGAACATCTATCAAGAACTGTATAAATAC TTTAATGATAAATCCGACAAGGAACTTTCTGACGAGGCTGCAAAATTGAAGAACGT AGTGGGACACCATGAGGCCGCAACCAATATAGTAAAGGATTACAGATACACTTATG ATAAGTATTTCCTCCATATGCCGATCACGATTAATTTCAAGGCGAATAAAACCGGCT TCATTAACGATCGCATTTTGCAATATATTGCGAAGGAAAAGGATTTGCACGTGATAG GTATAGACCGGGGTGAACGAAACTTGATTTACGTCTCTGTGATCGACACATGCGGAA ATATAGTTGAACAGAAGTCCTTTAATATTGTGAATGGTTACGACTACCAGATAAAAT TGAAGCAACAGGAGGGCGCAAGACAGATAGCTCGCAAAGAGTGGAAGGAAATCGG CAAGATCAAAGAAATAAAGGAGGGTTATCTTTCCCTGGTAATTCATGAAATTAGCA AGATGGTTATTAAGTATAATGCTATAATAGCTATGGAGGACCTTTCCTATGGGTTCA AGAAAGGTCGCTTCAAAGTGGAGCGACAAGTGTATCAAAAGTTCGAGACTATGTTG ATAAATAAATTGAATTATTTGGTTTTTAAAGACATTTCAATAACTGAGAACGGGGGT CTCTTGAAGGGGTACCAATTGACTTATATTCCGGACAAGTTGAAGAATGTCGGACAC CAGTGTGGTTGCATTTTCTACGTGCCTGCCGCTTACACCTCAAAAATCGATCCGACC ACTGGTTTTGTAAATATATTTAAATTCAAAGATCTCACCGTTGATGCCAAACGGGAG TTTATCAAAAAATTCGATTCCATTCGCTACGACTCTGAGAAAAACCTTTTTTGTTTCA CGTTCGATTATAACAACTTTATAACCCAAAATACTGTAATGTCCAAGTCAAGTTGGT CTGTCTATACTTACGGAGTAAGGATCAAGCGCCGCTTCGTTAATGGGAGATTCTCAA ACGAGTCTGATACCATAGACATAACTAAAGACATGGAAAAAACCCTGGAAATGACG GACATCAATTGGCGAGACGGGCATGATCTTCGACAGGACATAATAGATTACGAAAT TGTTCAACACATTTTCGAGATATTTCGACTTACGGTTCAGATGAGGAATTCCCTTTCC GAATTGGAAGACCGGGATTATGATCGACTTATATCTCCCGTGCTCAATGAAAACAAT ATTTTTTATGATTCAGCGAAAGCTGGGGACGCGCTGCCAAAAGATGCCGATGCCAAT GGAGCATACTGTATCGCCCTGAAGGGTTTGTATGAGATTAAGCAAATTACTGAAAAC TGGAAGGAAGATGGCAAGTTTTCTAGAGATAAGCTTAAGATTAGCAATAAGGACTG GTTTGACTTCATTCAAAATAAAAGGTATCTTAAACGTCCGGCAGCGACCAAAAAAG CCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAAAAA GAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 105 CCAGCGGCTAAAAAAAAGAAACTGGATGGCAGCGTGGATATGAATAATGGAACAA ATAATTTTCAAAATTTTATTGGTATCAGTTCATTGCAAAAGACTTTGAGAAATGCTTT GATCCCGACTGAGACCACACAGCAGTTCATCGTCAAAAATGGCATAATCAAGGAAG ACGAACTTAGGGGTGAGAATAGACAAATATTGAAGGACATCATGGATGACTATTAT AGGGGGTTCATTTCCGAAACGCTCAGTAGTATTGATGACATTGACTGGACTAGTCTT TTCGAGAAAATGGAAATTCAGCTTAAGAACGGGGACAATAAAGACACGCTGATCAA GGAGCAAACGGAATATAGGAAGGCGATCCATAAAAAATTCGCGAATGATGATCGGT TTAAAAACATGTTTAGTGCCAAGTTGATCAGCGACATACTGCCCGAATTCGTGATCC ACAACAATAATTACAGCGCCTCCGAAAAGGAGGAAAAAACTCAGGTCATTAAATTG TTTAGCCGATTCGCAACGAGTTTCAAAGATTATTTTAAGAACCGGGCCAACTGTTTT TCAGCGGATGATATTAGCTCCAGCAGCTGCCATCGCATAGTAAATGATAACGCTGAA ATCTTTTTTAGCAACGCACTTGTCTACCGGAGGATTGTAAAATCACTGTCAAATGAT GACATTAACAAAATATCTGGAGATATGAAGGACTCACTCAAAGAAATGAGCCTGGA AGAAATATATTCATACGAAAAATACGGGGAGTTTATTACCCAGGAAGGTATCAGTTT TTATAATGATATATGTGGAAAAGTTAATTCATTTATGAATCTTTACTGTCAAAAAAA TAAGGAGAACAAGAATTTGTACAAGCTCCAAAAACTTCATAAACAGATTCTGTGCA TCGCAGACACAAGTTATGAGGTACCGTACAAATTTGAGAGCGACGAAGAAGTTTAT CAGAGTGTGAATGGTTTCCTGGACAATATCTCTTCTAAACACATTGTTGAGAGGCTT AGGAAGATCGGTGATAATTATAACGGCTATAATCTGGACAAAATTTATATTGTATCA AAGTTTTATGAATCAGTCTCTCAAAAGACGTATCGGGATTGGGAAACAATTAACACG GCTCTGGAGATCCACTACAATAACATTCTGCCCGGCAACGGGAAGAGCAAAGCTGA TAAGGTCAAGAAGGCAGTCAAGAACGACCTTCAGAAGAGCATAACAGAAATTAACG AATTGGTCAGTAACTACAAACTGTGTAGTGATGACAACATAAAAGCCGAAACATAC ATCCATGAAATAAGCCATATCCTGAATAACTTCGAAGCCCAAGAACTTAAATACAAT CCCGAGATTCATCTTGTCGAATCAGAACTCAAGGCGTCCGAGCTCAAAAATGTCCTT GACGTGATAATGAATGCCTTCCACTGGTGCAGCGTATTCATGACGGAGGAGTTGGTA GATAAAGACAACAACTTTTATGCCGAATTGGAAGAGATTTATGATGAGATTTACCCC GTTATTTCTCTGTACAACTTGGTTCGAAACTACGTAACACAAAAACCATACTCAACC AAAAAGATCAAACTCAATTTTGGCATACCTACATTGGCTGATGGTTGGTCCAAGTCA AAGGAATATAGCAATAATGCAATAATTCTCATGCGAGATAACTTGTATTATTTGGGG ATCTTTAACGCTAAGAACAAACCAGATAAAAAGATAATCGAGGGGAACACAAGTGA GAACAAGGGTGATTACAAAAAAATGATTTACAATCTGCTTCCTGGGCCTAACAAAA TGATTCCGAAGGTGTTTCTTAGCTCTAAAACTGGAGTGGAGACGTATAAGCCTTCCG CGTACATTCTCGAAGGCTACAAGCAAAATAAGCATATCAAGTCCAGTAAGGACTTC GACATCACTTTTTGCCACGATCTCATCGATTACTTTAAGAACTGTATCGCAATACACC CCGAGTGGAAAAACTTTGGTTTTGATTTTTCAGACACTAGTACCTACGAGGACATTT CCGGCTTCTATCGAGAAGTCGAACTCCAGGGCTACAAAATCGATTGGACGTACATTT CTGAGAAGGACATCGACTTGCTCCAAGAGAAAGGTCAACTTTACCTCTTCCAAATTT ACAATAAAGACTTTTCAAAGAAGAGCACCGGTAATGACAACTTGCATACCATGTAT CTGAAGAACCTGTTTTCTGAGGAGAACCTCAAGGATATTGTATTGAAGTTGAATGGC GAAGCAGAAATATTTTTCCGAAAGTCATCTATCAAGAACCCCATTATACACAAAAA AGGCTCTATCCTGGTGAACCGGACTTACGAGGCAGAGGAGAAGGATCAATTCGGAA ACATACAGATAGTCCGCAAAAACATCCCTGAGAATATCTATCAGGAACTCTATAAGT ACTTCAATGATAAATCAGACAAGGAGCTTAGCGACGAAGCAGCTAAACTTAAAAAC GTGGTTGGCCATCACGAGGCCGCTACCAACATAGTCAAAGACTACCGCTATACTTAT GACAAGTACTTTTTGCACATGCCCATAACAATTAATTTCAAAGCTAACAAAACAGGG TTTATAAATGACAGAATCCTCCAATACATCGCCAAAGAGAAGGACCTCCATGTAATC GGGATTGATAGAGGCGAACGGAACTTGATTTACGTTAGTGTCATTGATACCTGTGGT AACATTGTCGAACAAAAGTCATTCAACATAGTCAATGGATATGATTATCAGATAAA ACTCAAGCAACAAGAAGGCGCGAGGCAGATTGCCAGGAAGGAATGGAAAGAAATC GGGAAGATCAAGGAGATCAAGGAGGGTTACCTGTCCTTGGTGATACACGAGATTTC AAAAATGGTTATAAAATACAATGCCATTATCGCGATGGAGGATTTGTCTTATGGATT TAAGAAGGGGAGGTTCAAAGTCGAACGACAAGTCTATCAGAAGTTTGAAACAATGC TCATTAACAAGCTCAATTACCTTGTTTTCAAGGATATAAGCATCACTGAAAACGGCG GACTCCTTAAGGGATATCAGCTGACTTATATCCCCGACAAGCTCAAGAACGTAGGGC ACCAATGCGGATGCATCTTTTACGTGCCTGCAGCATATACTTCAAAAATTGATCCGA CTACTGGCTTTGTTAACATTTTCAAGTTCAAGGATCTGACGGTAGACGCTAAGAGAG AATTCATAAAAAAGTTTGACAGCATCAGGTACGATAGTGAAAAGAACCTTTTTTGTT TTACCTTTGACTACAATAATTTTATTACGCAAAATACAGTTATGAGCAAATCAAGTT GGAGCGTTTACACATATGGCGTTCGGATCAAGCGCAGATTCGTCAATGGTCGCTTCT CAAATGAGAGCGATACAATCGATATAACGAAGGATATGGAGAAGACGCTTGAGATG ACAGATATCAACTGGCGGGACGGACATGACCTTAGACAAGACATAATCGATTACGA AATAGTACAGCATATCTTTGAGATTTTTAGGCTTACAGTTCAGATGCGGAACTCTCTT TCCGAACTGGAGGACCGGGATTATGATCGGTTGATCTCCCCAGTACTGAACGAAAAT AATATCTTTTACGATAGCGCGAAGGCTGGTGATGCACTCCCAAAAGACGCTGATGCG AACGGAGCTTATTGCATAGCCCTTAAAGGGCTTTACGAGATTAAACAAATAACAGA AAATTGGAAGGAAGATGGCAAATTTTCCCGCGACAAGTTGAAGATTAGTAACAAAG ACTGGTTCGACTTCATTCAGAATAAACGCTACCTCAAACGTCCGGCAGCGACCAAAA AAGCCGGCCAGGCGAAGAAAAAAAAAGCGTCAGGTAGCGGCGCAGGCAGCCCGAA AAAGAAACGTAAAGTCGAGGATCCGAAAAAGAAACGTAAGGTTATTCCGGGCTAA SEQ ID NO: 113 ATGGGCCATCATCATCATCATCATAGCAGCGGCGTGGATCTGGGCACCGAAAACCT GTATTTTCAGTCCATGAGCCGCCGCCGCAAAGCGAACCCGACCAAACTGAGCGAAA ACGCGAAAAAACTGGCGAAAGAAGTGGAAAACGCAAGCGGCAGCGGCGCGGGCAG CAAACGACCGGCGGCGACCAAAAAAGCGGGCCAAGCGAAGAAAAAGAAAGCAAGC GGCAGCGGCGCGGGCAGCCCGGCGGCAAAAAAAAAAAAACTGGACGGCAGCGTGG ATGCAAGCGGCAGCGGCGCGGGCAGCCCCAAAAAAAAACGCAAAGTTGAAGATGC AAGCGGCAGCGGCGCGGGCAGCCCGAAAAAAAAACGTAAAGTGGCAAGCGGCAGC GGCGCGGGCAGCATGAACAACGGCACCAACAACTTTCAGAACTTTATTGGCATTAG CAGCCTGCAGAAAACCCTGCGCAACGCGCTGATTCCGACCGAAACCACGCAGCAGT TTATTGTGAAAAACGGCATTATTAAAGAAGATGAACTGCGCGGCGAAAACCGTCAG ATTCTGAAGGACATTATGGATGATTATTATCGCGGCTTTATTAGCGAAACCCTGAGC AGCATTGATGATATAGACTGGACGAGCCTGTTTGAAAAAATGGAAATTCAGCTGAA AAACGGCGATAACAAAGATACCCTGATTAAAGAACAGACCGAATATCGCAAAGCGA TTCATAAGAAGTTTGCGAACGATGATCGCTTTAAAAACATGTTTAGCGCGAAACTGA TTAGCGATATTCTGCCGGAATTTGTGATTCATAACAACAACTATAGCGCGAGCGAAA AGGAAGAAAAAACCCAAGTGATTAAACTGTTTAGCCGCTTTGCGACGAGCTTTAAA GATTATTTTAAAAATCGCGCGAACTGCTTTAGCGCGGATGATATTAGCAGCAGCAGC TGCCATCGCATTGTGAACGATAACGCGGAGATCTTTTTTAGCAATGCGCTGGTGTAT CGCCGCATTGTGAAAAGCCTGAGCAACGATGATATTAACAAAATTAGCGGCGATAT GAAAGATAGCCTGAAAGAAATGAGCCTGGAAGAAATATATAGCTATGAAAAATATG GGGAATTTATTACACAAGAGGGCATTAGCTTTTATAACGATATTTGCGGCAAAGTGA ACAGCTTTATGAACCTGTATTGTCAGAAAAACAAAGAAAACAAAAACCTGTATAAA CTGCAGAAACTGCATAAACAGATTCTGTGCATTGCGGATACGAGCTATGAAGTGCC GTATAAATTTGAAAGCGATGAAGAAGTGTATCAGAGCGTGAACGGCTTTCTGGATA ACATTAGCAGCAAACATATTGTGGAACGCCTGCGCAAAATTGGCGATAACTATAAC GGCTATAACCTGGATAAAATTTATATTGTGAGCAAATTTTATGAAAGCGTGAGTCAG AAAACCTATCGCGATTGGGAAACCATTAACACCGCGCTGGAAATTCATTATAACAA CATTCTGCCGGGCAACGGCAAAAGTAAAGCGGATAAAGTGAAAAAAGCGGTGAAA AACGATCTGCAGAAAAGCATTACGGAAATTAACGAACTGGTGAGCAACTATAAACT GTGCAGCGATGATAACATTAAAGCGGAAACCTATATTCACGAGATCAGTCATATTCT GAACAACTTTGAAGCGCAAGAACTGAAATATAACCCGGAAATTCATCTGGTGGAAT CAGAACTGAAGGCGAGCGAACTTAAGAATGTGCTAGATGTGATTATGAACGCGTTT CATTGGTGCAGCGTGTTTATGACCGAAGAACTGGTGGATAAAGATAACAACTTTTAT GCGGAACTGGAAGAAATCTACGACGAAATTTATCCGGTGATTAGCCTGTATAACCTG GTGCGCAACTATGTGACGCAGAAACCGTATAGCACCAAAAAAATTAAACTGAACTT TGGCATTCCGACCCTGGCGGATGGCTGGAGCAAGAGCAAAGAGTATAGCAACAACG CTATTATCCTAATGCGCGATAACCTGTATTATCTGGGCATTTTTAACGCGAAAAACA AACCGGATAAAAAAATTATTGAAGGCAACACGAGCGAAAACAAAGGCGATTATAA AAAAATGATTTATAACCTGCTGCCGGGCCCGAACAAAATGATTCCGAAAGTGTTTCT GAGCAGCAAAACCGGCGTGGAAACCTATAAACCGAGCGCGTATATTCTGGAAGGCT ATAAACAGAACAAACATATTAAAAGCAGCAAAGATTTTGATATTACCTTTTGCCATG ATCTGATTGACTACTTTAAGAACTGTATAGCGATTCATCCGGAATGGAAAAACTTTG GCTTTGATTTTAGCGATACGAGCACCTATGAAGACATTAGCGGCTTTTATCGCGAAG TGGAACTGCAAGGCTATAAAATTGATTGGACCTATATTAGCGAAAAAGATATTGATC TGCTGCAAGAAAAAGGTCAGCTGTATCTGTTTCAGATTTATAACAAAGATTTTAGCA AAAAAAGCACCGGCAACGATAACCTGCATACCATGTATCTGAAAAATCTGTTTTCTG AAGAAAACCTAAAAGATATTGTCCTGAAACTGAACGGCGAAGCCGAAATTTTTTTTC GCAAGAGCAGCATTAAAAACCCGATTATTCACAAAAAAGGTAGCATTCTGGTGAAC CGCACATACGAAGCTGAGGAAAAGGATCAGTTTGGCAACATTCAGATTGTGCGCAA AAACATTCCGGAAAACATCTACCAAGAACTGTACAAATATTTTAACGATAAAAGCG ATAAAGAACTGAGCGACGAGGCTGCGAAGCTGAAGAATGTCGTGGGCCATCATGAA GCGGCGACTAACATTGTCAAAGATTATCGCTATACCTATGATAAATATTTTCTGCAT ATGCCGATTACCATTAACTTTAAAGCGAACAAAACCGGCTTTATTAACGATCGCATT CTGCAGTATATTGCGAAGGAAAAGGATCTGCACGTGATTGGCATTGATCGCGGCGA ACGCAACCTGATTTATGTGAGCGTGATTGATACCTGCGGCAACATTGTGGAACAGAA AAGCTTTAACATCGTGAACGGCTATGATTATCAGATTAAACTGAAACAGCAAGAAG GCGCGCGTCAGATTGCGCGCAAAGAATGGAAAGAAATTGGCAAAATTAAAGAAATT AAAGAAGGCTATCTGAGCCTGGTGATTCATGAAATCAGCAAGATGGTGATTAAATA TAATGCCATTATTGCGATGGAAGATCTGAGCTATGGCTTTAAAAAAGGCCGCTTTAA AGTGGAACGCCAAGTGTATCAGAAATTTGAAACCATGCTGATTAACAAACTGAACT ATCTGGTGTTTAAAGATATTAGTATTACTGAAAATGGCGGCCTGCTGAAAGGCTATC AGCTGACCTATATTCCGGACAAGCTGAAGAATGTGGGCCATCAGTGCGGCTGCATTT TTTATGTGCCGGCGGCGTATACGAGCAAAATTGATCCGACCACCGGCTTTGTGAACA TTTTTAAATTTAAAGATCTGACCGTGGATGCGAAACGGGAATTCATAAAAAAATTTG ATAGCATTCGCTATGATAGCGAAAAGAATCTGTTTTGCTTCACCTTTGATTATAACA ACTTTATAACGCAGAACACCGTGATGAGCAAAAGCAGCTGGAGCGTGTATACCTAT GGCGTGCGCATTAAACGCCGCTTTGTGAACGGCCGCTTTAGCAACGAAAGCGATAC CATTGATATTACCAAAGATATGGAAAAAACCCTGGAAATGACCGATATTAACTGGC GCGATGGCCATGATCTGCGCCAAGATATTATTGATTATGAAATTGTGCAGCATATTT TTGAAATTTTTCGCCTGACCGTGCAGATGCGCAACAGCCTGAGCGAACTGGAAGATC GCGATTATGATCGCCTGATTAGCCCGGTGCTGAACGAAAACAACATTTTTTATGATA GCGCGAAAGCGGGCGATGCGCTGCCGAAAGATGCGGATGCGAACGGCGCGTATTGC ATTGCGCTGAAAGGCCTGTATGAAATTAAACAGATTACGGAAAACTGGAAAGAAGA TGGCAAATTTAGCCGCGACAAGCTGAAAATTAGCAACAAAGATTGGTTTGATTTTAT TCAGAACAAACGCTATCTGTA

In certain embodiments, a nucleic acid-guided nuclease, e.g., Type V, preferably Type VA CRISPR nuclease polypeptide disclosed herein includes a polypeptide having an amino acid sequence of at least 50% identity to SEQ ID NO:2. In certain embodiments, a nucleic acid-guided nuclease, e.g., Type V, preferably Type VA CRISPR nuclease polypeptide disclosed herein includes a polypeptide having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity, preferably at least 80%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% identical to amino acid sequence of SEQ ID NO:2. In certain embodiments, a nucleic acid-guided nuclease, e.g., Type V, preferably Type VA CRISPR nuclease polypeptide disclosed herein includes a polypeptide having an amino acid sequence of at least 50% identity to SEQ ID NO: 3. In certain embodiments, a nucleic acid-guided nuclease, e.g., Type V, preferably Type VA CRISPR nuclease polypeptide disclosed herein includes a polypeptide having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity, preferably at least 80%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% identical, to amino acid sequence of SEQ ID NO: 3. In certain embodiments, a nucleic acid-guided nuclease, e.g., Type V, preferably Type VA CRISPR nuclease polypeptide disclosed herein includes a polypeptide having an amino acid sequence of at least 50% identity to SEQ ID NO: 4. In certain embodiments, a nucleic acid-guided nuclease disclosed herein includes a polypeptide having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity, preferably at least 80%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% identical to amino acid sequences of SEQ ID NO: 4. In certain embodiments, a nucleic acid-guided nuclease, e.g., Type V, preferably Type VA CRISPR nuclease polypeptide disclosed herein includes a polypeptide having an amino acid sequence of at least 50% identity to any one of SEQ ID NOs: 109-112. In certain embodiments, a nucleic acid-guided nuclease disclosed herein includes a polypeptide having an amino acid sequence at least 60, 70, 80, 85, 90, 95, 98, 99%, or 100%, identical, preferably at least 80%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% identical to amino acid sequence of any one of SEQ ID NOs: 109-112. In certain embodiments, a nucleic acid-guided nuclease, e.g., Type V, preferably Type VA CRISPR nuclease polypeptide disclosed herein includes a polypeptide having an amino acid sequence of at least 50% identity to SEQ ID NO: 109. In certain embodiments, a nucleic acid-guided nuclease disclosed herein includes a polypeptide having an amino acid sequence at least 60, 70, 80, 85, 90, 95, 98, 99%, or 100%, identical, preferably at least 80%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% identical to SEQ ID NO: 109. In certain embodiments, a nucleic acid-guided nuclease, e.g., Type V, preferably Type VA CRISPR nuclease polypeptide disclosed herein includes a polypeptide having an amino acid sequence of at least 50% identity to SEQ ID NO: 110. In certain embodiments, a nucleic acid-guided nuclease disclosed herein includes a polypeptide having an amino acid sequence at least 60, 70, 80, 85, 90, 95, 98, 99%, or 100%, identical, preferably at least 80%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% identical to SEQ ID NO: 110. In certain embodiments, a nucleic acid-guided nuclease, e.g., Type V, preferably Type VA CRISPR nuclease polypeptide disclosed herein includes a polypeptide having an amino acid sequence of at least 50% identity to SEQ ID NO: 111. In certain embodiments, a nucleic acid-guided nuclease disclosed herein includes a polypeptide having an amino acid sequence at least 60, 70, 80, 85, 90, 95, 98, 99%, or 100%, identical, preferably at least 80%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% identical to SEQ ID NO: 111. In certain embodiments, a nucleic acid-guided nuclease, e.g., Type V, preferably Type VA CRISPR nuclease polypeptide disclosed herein includes a polypeptide having an amino acid sequence of at least 50% identity to SEQ ID NO: 112. In certain embodiments, a nucleic acid-guided nuclease disclosed herein includes a polypeptide having an amino acid sequence at least 60, 70, 80, 85, 90, 95, 98, 99%, or 100%, identical, preferably at least 80%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% identical to SEQ ID NO: 112.

Nuclear Localization Signals (NLSs)

In certain embodiments, a composition, e.g., nuclease, disclosed herein includes one or more nuclear localization sequences (NLSs), such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more NLSs. In some embodiments, a composition, e.g., engineered nuclease comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more NLSs at or near the amino-terminus, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more NLSs at or near the carboxy-terminus, or a combination of these (e.g. one or more NLS at the amino-terminus and one or more NLS at the carboxy terminus). When more than one NLS is present, each may be selected independently of the others, such that a single NLS may be present in more than one copy and/or in combination with one or more other NLSs present in one or more copies. In certain embodiments the engineered nuclease comprises 4 NLSs.

Non-limiting examples of NLSs include an NLS sequence derived from: the NLS of the SV40 virus large T-antigen, having the amino acid sequence PKKKRKV (SEQ ID NO:5); the NLS from nucleoplasmin (e.g. the nucleoplasmin bipartite NLS with the sequence KRPAATKKAGQAKKKK (SEQ ID NO:6); the c-myc NLS having the amino acid sequence PAAKRVKLD SEQ ID NO:7) or RQRRNELKRSP (SEQ ID NO:8); the hRNPA1 M9 NLS having the sequence NQSSNFGPMKGGNFGGRSSGPYGGGGQYFAKPRNQGGY (SEQ ID NO:9); the sequence RMRIZFKNKGKDTAELRRRRVEVSVELRKAKKDEQILKRRNV (SEQ ID NO:10) of the IBB domain from importin-alpha; the sequences VSRKRPRP (SEQ ID NO:11) and PPKKARED (SEQ ID NO:12) of the myoma T protein; the sequence PQPKKKPL (SEQ ID NO:13) of human p53; the sequence SALI AP (SEQ ID NO:14) of mouse c-abl IV; the sequences DRLRR (SEQ ID NO:15) and PKQKKRK (SEQ ID NO:16) of the influenza virus NS1; the sequence RKLKKKIKKL (SEQ ID NO:17) of the Hepatitis virus delta antigen; the sequence REKKKFLKRR (SEQ ID NO:18) of the mouse Mx1 protein; the sequence KRKGDEVDGVDEVAKKKSKK (SEQ ID NO:19) of the human poly(ADP-ribose) polymerase; the sequence RKCLQAGMNLEARKTKK (SEQ ID NO:20) of the steroid hormone receptors (human) glucocorticoid; and EGL-13, MSRRRKANPTKLSENAKKLAKEVEN, SEQ ID NO: 107.

In certain embodiments, a nuclease provided herein comprises at least one myc-related NLS comprising the sequence PAAKKKKLD (SEQ ID NO:21); in certain embodiments the myc-related NLS is at the N-terminus of the nuclease. In certain embodiments, a nuclease provided herein comprises at least one nucleoplasmin NLS comprising the sequence KRPAATKKAGQAKKKK (SEQ ID NO:6); in certain embodiments the nucleoplasmin NLS is at the C-terminus of the nuclease. In certain embodiments a nuclease provided herein comprises at least one, or at least two, SV40 NLS sequences comprising the sequence PKKKRKV (SEQ ID NO:5); in certain embodiments the SV40 NLSs are at the C-terminus of the nuclease. In certain embodiments, a nuclease provided herein comprises 1 NLS at the N-terminus and 3 NLSs at the C-terminus, for example 1 myc-related NLS at the N-terminus and one nucleoplasmin NLS and two SV40 NLSs at the C-terminus. In certain embodiments, a nuclease provided herein comprises 1 myc-related NLS at the N-terminus with the sequence PAAKKKKLD (SEQ ID NO:21 and one nucleoplasmin NLS comprising the sequence KRPAATKKAGQAKKKK (SEQ ID NO:6) and two SV40 NLSs comprising the sequence PKKKRKV (SEQ ID NO:5) at the C-terminus.

In general, the one or more NLSs are of sufficient strength to drive accumulation of the nucleic acid-guided nuclease in a detectable amount in the nucleus of a eukaryotic cell. In general, strength of nuclear localization activity may derive from the number of NLSs, the particular NLS(s) used, or a combination of these factors. Detection of accumulation in the nucleus may be performed by any suitable technique. For example, a detectable marker may be fused to the nucleic acid-guided nuclease, such that location within a cell may be visualized, such as in combination with a means for detecting the location of the nucleus (e.g. a stain specific for the nucleus such as DAPI). Cell nuclei may also be isolated from cells, the contents of which may then be analyzed by any suitable process for detecting protein, such as immunohistochemistry, Western blot, or enzyme activity assay. Accumulation in the nucleus may also be determined indirectly, such as by an assay for the effect of the nucleic acid-guided nuclease complex formation (e.g. assay for DNA cleavage or mutation at the target sequence, or assay for altered gene expression activity affected by targetable nuclease complex formation and/or nucleic acid-guided nuclease activity), as compared to a control not exposed to the nucleic acid-guided nuclease or targetable nuclease complex, or exposed to a nucleic acid-guided nuclease lacking the one or more NLSs.

In certain embodiments, a nucleic acid-guided nuclease disclosed herein includes a polypeptide having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity to amino acid sequences of SEQ ID NO: 4 and at least one myc-related NLS comprising the sequence PAAKKKKLD (SEQ ID NO:21); in certain embodiments the myc-related NLS is at the N-terminus of the nuclease. In certain embodiments, a nucleic acid-guided nuclease disclosed herein includes a polypeptide having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity to amino acid sequences of SEQ ID NO: 4 and at least one nucleoplasmin NLS comprising the sequence KRPAATKKAGQAKKKK (SEQ ID NO:6); in certain embodiments the nucleoplasmin NLS is at the C-terminus of the nuclease. In certain embodiments, a nucleic acid-guided nuclease disclosed herein includes a polypeptide having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity to amino acid sequences of SEQ ID NO: 4 and at least one, or at least two, SV40 NLS sequences comprising the sequence PKKKRKV (SEQ ID NO: 5); in certain embodiments the SV40 NLSs are at the C-terminus of the nuclease. In certain embodiments, a nucleic acid-guided nuclease disclosed herein includes a polypeptide having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity to amino acid sequences of SEQ ID NO: 4 and one NLS at the N-terminus and three NLSs at the C-terminus, for example 1 myc-related NLS at the N-terminus and one nucleoplasmin NLS and two SV40 NLSs at the C-terminus. In certain embodiments, a nucleic acid-guided nuclease disclosed herein includes a polypeptide having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity to amino acid sequences of SEQ ID NO: 4, and one myc-related NLS at the N-terminus with the sequence PAAKKKKLD (SEQ ID NO:21) and one nucleoplasmin NLS comprising the sequence KRPAATKKAGQAKKKK (SEQ ID NO:6) and two SV40 NLSs comprising the sequence PKKKRKV (SEQ ID NO:5) at the C-terminus. In certain embodiments, a nucleic acid-guided nuclease disclosed herein includes a polypeptide having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity to amino acid sequences of SEQ ID NO: 1, and one, two, or three NLS at the N-terminus and one, two, or three NLS at the C-terminus. In certain embodiments, a nucleic acid-guided nuclease disclosed herein includes a polypeptide having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity to amino acid sequences of SEQ ID NO: 1, and one myc-related NLS at the N-terminus with the sequence PAAKKKKLD (SEQ ID NO:21) and one nucleoplasmin NLS comprising the sequence KRPAATKKAGQAKKKK (SEQ ID NO:6) and two SV40 NLSs comprising the sequence PKKKRKV (SEQ ID NO:5) at the C-terminus.

Purification Tags

In certain embodiments, a nucleic acid-guided nuclease provided herein can comprise a tag, e.g., a purification tag, e.g. at the N-terminus. Exemplary tags include a poly-his tag, such as a Gly-6×His tag (SEQ ID NO: 421) or Gly-8×His tag (SEQ ID NO: 422), short epitope tags such as FLAG, hemagglutinin (HA), c-myc, T7, and Glu-Glu; maltose binding protein (mbp); N-terminal glutathione S-transferase (GST); calmodulin binding peptide (CBP). In certain embodiments, a nucleic acid-guided nuclease provided herein can comprise a poly-his tag, such as a Gly-6×His tag (SEQ ID NO: 421), e.g., at the N-terminus. These Gly-6×His tags (SEQ ID NO: 421) are applied for several reasons including: 1) a 6×His tag (SEQ ID NO: 423) can be used in protein purification to allow binding to the chromatographic columns for purification, and 2) the N-terminal glycine allows further, site-specific, chemical modifications that permit advanced protein engineering. Further, the Gly-6×His (SEQ ID NO: 421) is designed for easy removal, if desired, by digestion with Tobacco Etch Virus (TEV) protease. For these constructs, the Gly-6×His tag (SEQ ID NO: 421) was positioned on the N-terminus. Gly-6×His tags (SEQ ID NO: 421) are further described in Martos-Maldonado et al., Nat Commun. (2018) 17;9(1):3307, the disclosure of which is incorporated herein. Thus, in certain embodiments provided herein is a nucleic acid-guided nuclease disclosed herein includes a polypeptide having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity to amino acid sequences of SEQ ID NO: 4 and a poly-His tag at the N-terminus, such as a Gly-6×His tag (SEQ ID NO: 421). In certain embodiments provided herein is a nucleic acid-guided nuclease disclosed herein includes a polypeptide having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity to amino acid sequences of SEQ ID NO: 4, a poly-His tag at the N-terminus, such as a Gly-6×His tag (SEQ ID NO: 421), and/or a TEV cleavage site at the N-terminus. In certain embodiments provided herein is a nucleic acid-guided nuclease having a poly-His tag at the N-terminus, such as a Gly-6×His tag (SEQ ID NO: 421) and a TEV cleavage site at the N-terminus, such as a polypeptide having at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity to amino acid sequences of SEQ ID NO: 2. In certain embodiments provided herein is a nucleic acid-guided nuclease disclosed herein includes a polypeptide having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity to amino acid sequences of SEQ ID NO: 1, a poly-His tag at the N-terminus, such as a Gly-6×His tag (SEQ ID NO: 421), and/or a TEV cleavage site at the N-terminus. Additionally or alternatively, the nuclease may comprise one or more NLS as described herein.

Cleavage Sites

In addition to, or alternatively to, including one or more NLSs, purification tags, and/or other additional amino acid sequences described herein, an engineered nuclease polypeptide disclosed herein can include one or more cleavage sites, which can be at or near the N-terminus or the C-terminus. Any suitable cleavage site can be used; if a plurality of cleavage sits is used, they may be the same or different. In certain embodiments a cleavage site comprises a Tobacco Etch Virus protease cleavage sequence, herein referred to as a “TEV sequence” (SEQ ID NO: 108). The TEV sequence can be at or near the amino terminus. Generally, the cleavage sequence, e.g., TEV sequence, is located so that cleavage at the cleavage sequence leaves other additional amino acid sequences, in particular any NLS added to the original nuclease polypeptide, intact. A TEV cleavage site can have the amino acid sequence ENLYFQS (SEQ ID. NO: 108.

In certain embodiments, provided herein is a nucleic acid sequence encoding a polypeptide having at least 50% nucleic acid identity to a polypeptide represented by SEQ ID NO: 2. In certain embodiments, provided herein is a nucleic acid sequence encoding a polypeptide having at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, greater than 95%, or 100% to a polypeptide represented by SEQ ID NO: 2. In certain embodiments, provided herein is a nucleic acid sequence encoding a polypeptide having at least at least 50% nucleic acid identity to a polypeptide represented by SEQ ID NO: 3. In certain embodiments, provided herein is a nucleic acid sequence encoding a polypeptide having at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, greater than 95%, or 100% to a polypeptide represented by SEQ ID NO: 3. In certain embodiments, provided herein is a nucleic acid sequence encoding a polypeptide having at least at least 50% nucleic acid identity to a polypeptide represented by SEQ ID NO: 4. In certain embodiments, provided herein is a nucleic acid sequence encoding a polypeptide having at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, greater than 95%, or 100% to a polypeptide represented by SEQ ID NO: 4. In certain embodiments, provided herein is a nucleic acid of at least about 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% polynucleotide identity to any one of SEQ ID NOS: 23-105. In certain embodiments, provided herein is a nucleic acid of at least about 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% polynucleotide identity to any one of SEQ ID NOS: 23-42 In certain embodiments, provided herein is a nucleic acid of at least about 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% polynucleotide identity to any one of SEQ ID NOS: 43-65. In certain embodiments, provided herein is a nucleic acid of at least about 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% polynucleotide identity to any one of SEQ ID NOS: 43-53. In certain embodiments, provided herein is a nucleic acid of at least about 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% polynucleotide identity to any one of SEQ ID NOS: 54-58. In certain embodiments, provided herein is a nucleic acid of at least about 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% polynucleotide identity to any one of SEQ ID NOS: 59-63. In certain embodiments, provided herein is a nucleic acid of at least about 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% polynucleotide identity to any one of SEQ ID NO: 43. In certain embodiments, provided herein is a nucleic acid of at least about 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% polynucleotide identity to any one of SEQ ID NOS: 64-84. In certain embodiments, provided herein is a nucleic acid of at least about 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% polynucleotide identity to any one of SEQ ID NO: 64. In certain embodiments, provided herein is a nucleic acid of at least about 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% polynucleotide identity to any one of SEQ ID NOS: 64-74. In certain embodiments, provided herein is a nucleic acid of at least about 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% polynucleotide identity to any one of SEQ ID NOS: 75-79. In certain embodiments, provided herein is a nucleic acid of at least about 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% polynucleotide identity to any one of SEQ ID NOS: 80-84. In certain embodiments, provided herein is a nucleic acid of at least about 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% polynucleotide identity to any one of SEQ ID NOS: 85-105. In certain embodiments, provided herein is a nucleic acid of at least about 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% polynucleotide identity to any one of SEQ ID NO: 85. In certain embodiments, provided herein is a nucleic acid of at least about 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% polynucleotide identity to any one of SEQ ID NOS: 85-95. In certain embodiments, provided herein is a nucleic acid of at least about 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% polynucleotide identity to any one of SEQ ID NOS: 96-100. In certain embodiments, provided herein is a nucleic acid of at least about 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% polynucleotide identity to any one of SEQ ID NOS: 101-105.

A nucleic acid sequence encoding a nucleic acid-guided nuclease can be operably linked to a promoter. Such nucleic acid sequences can be linear or circular. The nucleic acid sequences can be encompassed on a larger linear or circular nucleic acid sequences that comprises additional elements such as an origin of replication, selectable or screenable marker, terminator, other components of a targetable nuclease system, such as a guide nucleic acid, and/or an editing or recorder cassette as disclosed herein. In some aspects, nucleic acid sequences can include sequences that code for at least one glycine, at least one poly-histidine tag, such as a 6× histidine tag (SEQ ID NO: 423), and/or at least one, two, three, four, or five nuclear localization signal tags, some or all of which can be on the amino side of the polypeptide, the carboxy side of the polypeptide, or a combination thereof. Larger nucleic acid sequences can be recombinant expression vectors, as are described in more detail later.

Guide Nucleic Acids

In certain embodiments, compositions and methods disclosed herein include a guide nucleic acid (gNA), e.g., a gRNA.

In general, a guide polynucleotide, also referred to as a guide nucleic acid (gNA) can complex with a compatible nucleic acid-guided nuclease, such as those disclosed herein, and can hybridize with a target nucleic acid sequence, thereby directing the nuclease to the target nucleic acid sequence. A subject nucleic acid-guided nuclease capable of complexing with a guide polynucleotide can be referred to as a nucleic acid-guided nuclease that is compatible with the guide polynucleotide. In addition, a guide polynucleotide capable of complexing with a nucleic acid-guided nuclease can be referred to as a guide polynucleotide or a guide nucleic acid that is compatible with the nucleic acid-guided nuclease. In some embodiments, a polynucleotide (gRNA) disclosed herein can be split into fragments, e.g., two separate polynucleotides, in some cases encompassing a synthetic tracrRNA and crRNA. Such gNAs, e.g., gRNAs, can be referred to as dual or split gNA, e.g., gRNA.

A guide polynucleotide can be DNA. A guide polynucleotide can be RNA. A guide polynucleotide can include both DNA and RNA. A guide polynucleotide can include modified or non-naturally occurring nucleotides. In cases where the guide polynucleotide comprises RNA, the RNA guide polynucleotide can be encoded by a DNA sequence on a polynucleotide molecule such as a plasmid, linear construct, or editing cassette as disclosed herein.

A guide polynucleotide can comprise a guide sequence, also referred to herein as a spacer sequence. A guide (spacer) sequence is a polynucleotide sequence having sufficient complementarity with a target polynucleotide sequence, also referred to herein as a target nucleic acid sequence, to hybridize with the target sequence and direct sequence-specific binding of a complexed nucleic acid-guided nuclease to the target sequence. The degree of complementarity between a guide sequence and its corresponding target sequence, when optimally aligned using a suitable alignment algorithm, is about or more than about 50%, 60%, 75%, 80%, 85%, 90%, 95%, 97.5%, 99%, or more. Optimal alignment may be determined with the use of any suitable algorithm for aligning sequences. In some embodiments, a guide sequence can be about or more than about 5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 75, or more nucleotides in length. In other embodiments, a guide sequence can be less than about 75, 50, 45, 40, 35, 30, 25, 20 nucleotides in length. Preferably the guide sequence is 10-30 nucleotides long. The guide sequence can be 15-20 nucleotides in length. The guide sequence can be 15 nucleotides in length. The guide sequence can be 16 nucleotides in length. The guide sequence can be 17 nucleotides in length. The guide sequence can be 18 nucleotides in length. The guide sequence can be 19 nucleotides in length. The guide sequence can be 20 nucleotides in length.

A guide polynucleotide can include a scaffold sequence. In general, a “scaffold sequence” can include any sequence that has sufficient sequence to promote formation of a targetable nuclease complex, wherein the targetable nuclease complex includes, but is not limited to, a nucleic acid-guided nuclease and a guide polynucleotide that can include a scaffold sequence and a guide sequence. Sufficient sequence within the scaffold sequence to promote formation of a targetable nuclease complex may include a degree of complementarity along the length of two sequence regions within the scaffold sequence, such as one or two sequence regions involved in forming a secondary structure. In some cases, the one or two sequence regions are included or encoded on the same polynucleotide. In some cases, the one or two sequence regions are included or encoded on separate polynucleotides. Optimal alignment may be determined by any suitable alignment algorithm, and may further account for secondary structures, such as self-complementarity within either the one or two sequence regions. In some embodiments, the degree of complementarity between the one or two sequence regions along the length of the shorter of the two when optimally aligned is about or more than about 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 97.5%, 99%, or higher. In some embodiments, at least one of the two sequence regions can be about or more than about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 40, 50, or more nucleotides in length.

A scaffold sequence of a subject guide polynucleotide can comprise a secondary structure. A secondary structure can comprise a pseudoknot region. In some cases, binding kinetics of a guide polynucleotide to a nucleic acid-guided nuclease is determined in part by secondary structures within the scaffold sequence. In some cases, binding kinetics of a guide polynucleotide to a nucleic acid-guided nuclease is determined in part by nucleic acid sequence with the scaffold sequence. In some aspects, the invention provides a nuclease that binds to a guide polynucleotide can include a conserved scaffold sequence. For example, the nucleic acid-guided nucleases for use in the present disclosure can bind to a conserved pseudoknot region.

In certain embodiments, the engineered polynucleotide (gRNA) can be split into fragments encompassing a synthetic tracrRNA and crRNA.

As used herein, “guide nucleic acid” or “guide polynucleotide” can refer to one or more polynucleotides and can include 1) a guide (spacer) sequence capable of hybridizing to a target sequence and 2) a scaffold sequence capable of interacting with or complexing with a nucleic acid-guided nuclease as described herein. A guide nucleic acid can be provided as one or more nucleic acids. In specific embodiments, the guide sequence and the scaffold sequence are provided as a single polynucleotide. In other aspects, guide nucleic acid may include at least one amplicon targeting fragments.

A guide nucleic acid can be compatible with a nucleic acid-guided nuclease when the two elements can form a functional targetable nuclease complex capable of cleaving a target sequence. In certain methods, a compatible scaffold sequence for a compatible guide nucleic acid can be found by scanning sequences adjacent to a native nucleic acid-guided nuclease loci.

For example, native nucleic acid-guided nucleases can be encoded on a genome within proximity to a corresponding compatible guide nucleic acid or scaffold sequence.

Nucleic acid-guided nucleases can be compatible with guide nucleic acids that are not found within the nucleases endogenous host. Such orthogonal guide nucleic acids can be determined by empirical testing. Orthogonal guide nucleic acids can come from different bacterial species or be synthetic or otherwise engineered to be non-naturally occurring.

Orthogonal guide nucleic acids that are compatible with a common nucleic acid-guided nuclease can comprise one or more common features. Common features can include sequence outside a pseudoknot region. Common features can include a pseudoknot region. Common features can include a primary sequence or secondary structure.

A guide nucleic acid can be engineered to target a desired target sequence by altering the guide (spacer) sequence such that the guide sequence is complementary to the target sequence, thereby allowing hybridization between the guide sequence and the target sequence. A guide nucleic acid with an engineered guide sequence can be referred to as an engineered guide nucleic acid. Engineered guide nucleic acids are often non-naturally occurring and are not found in nature.

Engineered guide nucleic acids can be formed using a Synthetic Tracr RNA (STAR) system. STAR, when combined with a Cas12a protein, can form at least one ribonucleoprotein (RNP) complex that targets a specific genomic locus. STAR takes advantage of the natural properties of the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) where the CRISPR system functions much like an immune system against invading viruses and plasmid DNA. Short DNA sequences (spacers) from invading viruses are incorporated at CRISPR loci within the bacterial genome and serve as “memory” of previous infections. Reinfection triggers complementary mature CRISPR RNA (crRNA) to find a matching viral sequence. Together, the crRNA and trans-activating crRNA (tracrRNA) guide CRISPR-associated (Cas) nuclease to cleave double-strand breaks in “foreign” DNA sequences. The prokaryotic CRISPR “immune system” has been engineered to function as an RNA-guided, mammalian genome editing tool that is simple, easy and quick to implement. STAR (which includes synthetic crRNA and tracrRNA) when combined with Cas12a protein can form ribonucleoprotein (RNP) complexes that target a specific genomic locus. Engineered guide nucleic acids formed with the RNA (STAR) system can result in a split gRNA. Split gRNA, i.e., dual guide RNAs are described more fully in WO 2021067788A1.

In certain embodiments, provided herein are ribonucleoprotein (RNP) complexes that include at least one nuclease disclosed herein. In certain embodiments, a RNP complex can include at least one nuclease having an amino acid sequence of at least 50% identity to SEQ ID NO:2. In certain embodiments, a RNP complex can include at least one nuclease having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity to amino acid sequences of SEQ ID NO:2. In certain embodiments, a RNP complex can include at least one nuclease having an amino acid sequence of at least 50% identity to SEQ ID NO:3. In certain embodiments, a RNP complex can include at least one nuclease having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity to amino acid sequences of SEQ ID NO:3. In certain embodiments, a RNP complex can include at least one nuclease having an amino acid sequence of at least 50% identity to SEQ ID NO:4. In certain embodiments, a RNP complex can include at least one nuclease having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity to amino acid sequences of SEQ ID NO:4. In certain embodiments, a RNP complex including a nuclease disclosed herein can further include at least one STAR gRNA (dual guide RNA). In certain embodiments, a RNP complex including a nuclease disclosed herein can further include at least one non-STAR gRNA (e.g., single guide RNA). In certain embodiments, a RNP complex including a nuclease disclosed herein can further include at least one polynucleotide. In certain embodiments, a polynucleotide included in a RNP complex disclosed herein can be greater than about 50 nucleotides in length. In certain embodiments, a polynucleotide included in a RNP complex disclosed herein can be about 50, to about 150, to about 500, to about 1000 nucleotides, or greater than 1000 nucleotides in length. In certain embodiments, more than one nuclease can be added to an RNP complex to affect the overall editing efficiency. In certain embodiments, more than one gRNA can be added to the RNP complex to allow for multiplexed editing of more than one site in a single transfection for improved efficiency. In other embodiments, more than one DNA template can be added to the RNP to allow for multiplexed editing at one or more sites based on a specific desired repair outcome.

In certain embodiments, a composition comprising a Type V, e.g., Type VA, CRISPR nuclease polypeptide, such as described herein, further comprises a guide nucleic acid (gNA), e.g., gRNA, comprising a spacer sequence that targets a target nucleotide sequence (also referred to herein as a target nucleic acid sequence) within a polynucleotide (also referred to herein as a target polynucleotide, as will be clear from context), or a polynucleotide coding for the gNA, e.g., gRNA, wherein the gNA, e.g., gRNA is compatible with the Type V, e.g., Type VA, CRISPR nuclease. In general, a polynucleotide within which a target target nucleotide sequence (target nucleic acid sequence) is located, as that term is used herein, includes a polynucleotide that includes the target target nucleotide sequence (target nucleic acid sequence). Such a polynucleotide can be any suitable polynucleotide, such as a genome of a cell or part of a genome of a cell. In certain embodiments, the target nucleotide sequence (target nucleic acid sequence) is within 50 nucleotides of a protospacer adjacent motif (PAM) sequence specific for the Type V CRISPR nuclease, such as a PAM comprising a sequence of YTTN, wherein Y is T or C and N is A, T, G, or C, or a sequence of YTTV or TTTV, wherein V is A, G, or C. In certain embodiments the PAM comprises a sequence of YTTV or TTTV, wherein V is A, G, or C. In certain embodiments, the gNA is a gRNA, such as a dual (split) gRNA. The gNA, e.g. gRNA, can comprise one or more chemical modifications, such as 2′-O-alkyl, a 2′-O-methyl, a phosphorothioate, a phosphonoacetate, a thiophosphonoacetate, a 2′-O-methyl-3′-phosphorothioate, a 2′-O-methyl-3′-phosphonoacetate, a 2′-O-methyl-3′-thiophosphonoacetate, a 2′-deoxy-3′-phosphonoacetate, a 2′-deoxy-3′-thiophosphonoacetate, a suitable alternative, or a combination thereof. In certain embodiments, a ratio of guanine:uracil in the gRNA is at least 51:49, 52:48, 53:47, 54:46, 55:45, 56:44, 57:43, 58:42, 59:42, or 60:40, preferably at least 53:47, more preferably at least 54:46, even more preferably at least 55:45. See Example 12 and FIG. 10 . In certain embodiments, a molar ratio of gNA, e.g., gRNA to Type V CRISPR nuclease is at least 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 2:1, 2.2:1, 2.5:1, or 3:1 and/or not more than 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 2:1, 2.2:1, 2.5:1, 3:1, or 4:1, preferably 1.1:1 to 2.5:1, more preferably 1.2:1 to 2:1, even more preferably 1.2:1 to 1.7:1. See, e.g., Example 13. In certain embodiments a molar amount of gNA, e.g., gRNA, is at least 10, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 170, 190 or 200 pmol and/or not more than 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 170, 190, 200, 250, or 300 pmol, preferably 25-200 pmol, more preferably 50-100 pmol, even more preferably 65 to 85 pmol. See Example 13.

In certain embodiments, a composition comprising a Type V, e.g., Type VA, CRISPR nuclease polypeptide, such as described herein, further includes a donor template, also referred to as an editing template herein. A donor template can comprise homology arms, that is, nucleotide sequences that are complementary with polynucleotide sequences on either side of a cleavage site at which the donor template will be inserted. The donor template can be present in any suitable amount, e.g., in certain embodiments, at least 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.7, 2, 2.5, 3, 4, or 5 μg μL⁻¹ and/or not more than 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.7, 2, 2.5, 3, 4, 5, 7, or 10 μg μL⁻¹, preferably 0.3 to 2 μg μL⁻¹, more preferably 0.5 to 1.5 μg μL⁻¹, even more preferably 0.8 to 1.2 μg μL⁻¹.

In certain embodiments, a composition comprising a Type V, e.g., Type VA, CRISPR nuclease polypeptide, such as described herein, further includes an anionic polymer. Any suitable anionic polymer may be used. Exemplary anionic polymers include 1,2,3-heptanetriol, 2-Amino-2-(hydroxymethyl)-1,3-propanediol (Tris), 3-(1-pyridino)-1-propane sulfonate (NDSB 201), 3[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), 6-aminocaproic acid, adenosine diphosphate (ADP), adenosine triphosphate (ATP), alpha-cyclodextrin, amidosulfobetaine-14 (ASB-14), ammonium acetate, ammonium nitrate, ammonium sulfate, arginine, arginine ethylester, barium chloride, barium iodide, benzamidine HCl, beta-cyclodextrin, beta-mercaptoethanol (BME), biotin, calcium chloride, cesium chloride, cesium sulfate, cetyltrimethylammonium bromide (CTAB), choline chloride, citric acid, cobalt chloride, copper (II) chloride, cyclohexanol, D-sorbitol, dimethylethylammoniumpropane sulfonate (NDSB 195), dithiothreitol (DTT), erythritol, ethanol, ethylene glycol, ethylene glycol-bis(βbeta-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA), ethylenediaminetetraacetic acid (EDTA), formamide, gadolinium bromide, gamma butyrolactone, glucose, glutamic acid, glutamine, glycerol, glycine, glycine betaine, glycine-glycine-glycine, guanidine HCl, guanosine triphosphate (GTP), holmium chloride, imidazole, iron (III) chloride, Jeffamine M-600, lanthanum acetate, lauryl sulfobetaine, lauryldimethylamine N-oxide (LDAO), lithium sulfate, magnesium chloride, magnesium sulfate, manganese chloride, mannitol, N-(2-hydroxyethyl)piperazine-N′-(3-propanesulfonic acid) (EPPS), N-dodecyl beta-D-maltoside (DDM), N-ethylurea, n-hexanol, N-lauryl sarcoside, N-lauryl sarcosine, N-methylformamide, N-methylurea, n-octyl-b-D-glucoside (OG: Octyl glucoside), n-penthanol, nickel chloride, non-detergent sulfo betaine (NDSB), Nonidet P40 (NP40), octyl beta-D-glucopyranoside, poly-L-glutamic acid, polyethylene glycol (for example, PEG 300, PEG 3350, PEG 4000), polyethyleneglycol lauryl ether (Brij 35), polyoxyethylene (2) oleyl ether (Brij 93), polyoxyethylene cetyl ether (Brij 56), polyvinylpyrrolidone 40 (PVP40), potassium chloride, potassium citrate, potassium nitrate, proline, putrescine, spermidine, spermine, riboflavin, samarium bromide, sarcosine, sodium acetate, sodium chloride, sodium dodecyl sulfate (SDS), sodium fluoride, sodium iodide, sodium lauroyl sarcosinate (Sarkosyl), sodium malonate, sodium molybdate, sodium selenite, sodium sulfate, sodium thiocyanate, sucrose, taurine, trehalose, tricine, triethylamine, trimethylamine N-oxide (TMAO), tris(2-carboxyethyl)phosphine (TCEP), Triton X-100, Tween 20, Tween 60, Tween 80, urea, vitamin B12, xylitol, yttrium chloride, yttrium nitrate, zinc chloride, Zwittergent 3-08, Zwittergent 3-14, or a combination thereof. In certain embodiments, an anionic polymer comprises polyglutamic acid. In certain embodiments, the anionic polymer, e.g., PGA, is present at a concentration of at least 20, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 170, 200, 250, 300, 400, or 500 μg μL⁻¹ and/or not more than 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 170, 200, 250, 300, 400, 500, 700, or 1000 μg μL⁻¹, preferably 20 to 200 μg μL⁻¹, more preferably 50 to 150 μg μL⁻¹, even more preferably 80 to 120 μg μL⁻¹ (PGA).

In certain embodiments, provided herein is a cell containing one or more of the compositions described herein, e.g. a composition comprising a Type V, e.g., Type VA, CRISPR nuclease polypeptide comprising one or more NLSs and, in certain embodiments a purification tag and/or cleavage site. Any suitable cell may be used. In certain embodiments the cell is a human cell, such as an immune cell, e.g., T cell, or a stem cell, e.g., induced pluripotent stem cell (iPSC).

In certain embodiments, provided herein are methods of inserting one or more of the compositions described herein, e.g., a composition comprising a Type V, e.g., Type VA, CRISPR nuclease polypeptide comprising one or more NLSs and, in certain embodiments a purification tag and/or cleavage site, into a cell. Any suitable method for insertion may be used. In certain embodiments, electroporation is used. Electroporation conditions can be optimized, see, e.g., Examples.

In certain embodiments provided are methods of modifying a target polynucleotide comprising contacting the target polynucleotide with a composition or compositions as described herein, e.g, a composition comprising a Type V, e.g., Type VA, CRISPR nuclease polypeptide comprising one or more NLSs and a suitable gNA, e.g., gRNA, and allowing the composition to modify the target polynucleotide, in some cases a genomic region, such as a genome or part of a genome within a cell, e.g. human cell such as an immune cell, e.g., T cell, or a stem cell, e.g., iPSC. In certain cases, the composition or compositions comprises a donor template, such as a donor template comprising a polynucleotide coding for a polypeptide to be expressed by the cell, in certain embodiments the polypeptide comprises a chimeric antigen receptor (CAR) or portion thereof; see, e.g., Examples. In certain embodiments the cell is a human cell, e.g., immune cell such as a T cell, or stem cell, such as an iPSC.

Nuclease Systems

In certain embodiments disclosed herein are targetable nuclease systems. In certain embodiments, targetable nuclease system can include a nucleic acid-guided nuclease and a compatible guide nucleic acid (also referred to interchangeably herein as “guide polynucleotide” and “gRNA”). A targetable nuclease system can include a nucleic acid-guided nuclease or a polynucleotide sequence encoding the nucleic acid-guided nuclease. A targetable nuclease system can include a guide nucleic acid or a polynucleotide sequence encoding the guide nucleic acid.

In general, a targetable nuclease system as disclosed herein can be characterized by elements that promote the formation of a targetable nuclease complex at the site of a target sequence, wherein the targetable nuclease complex includes a nucleic acid-guided nuclease and a guide nucleic acid.

A guide nucleic acid together with a nucleic acid-guided nuclease forms a targetable nuclease complex which is capable of binding to a target sequence within a target polynucleotide, as determined by the guide sequence of the guide nucleic acid.

In general, to generate a double stranded break, in most cases a targetable nuclease complex binds to a target sequence as determined by the guide nucleic acid, and the nuclease has to recognize a protospacer adjacent motif (PAM) sequence adjacent to the target sequence.

A targetable nuclease complex can include a nucleic acid-guided nuclease having an amino acid sequence of at least 50% identity to SEQ ID NO: 2 and a compatible guide nucleic acid. A targetable nuclease complex can include a nucleic acid-guided nuclease having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity to amino acid sequences SEQ ID NO: 2 and a compatible guide nucleic acid. protospacer adjacent motif (PAM) sequence adjacent to the target sequence. A targetable nuclease complex can include a nucleic acid-guided nuclease having an amino acid sequence of at least 50% identity to SEQ ID NO: 3 and a compatible guide nucleic acid. A targetable nuclease complex can include a nucleic acid-guided nuclease having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity to amino acid sequences of SEQ ID NO: 3 and a compatible guide nucleic acid. A targetable nuclease complex can include a nucleic acid-guided nuclease having an amino acid sequence of at least 50% identity to SEQ ID NO: 4 and a compatible guide nucleic acid. A targetable nuclease complex can include a nucleic acid-guided nuclease having an amino acid sequence of at least about 60%, 65%, 75%, 85%, 95%, 99% or about 100% identity to amino acid sequences of SEQ ID NO: 4 and a compatible guide nucleic acid. In certain embodiments, the guide nucleic acid can include a scaffold sequence compatible with the nucleic acid-guided nuclease selected. In any of these embodiments, the guide sequence can be engineered to be complementary to any desired target sequence. The guide sequence selected can be engineered to hybridize to any desired target sequence. In certain embodiments, the guide sequence is a dual guide RNA.

A target sequence of a targetable nuclease complex can be any polynucleotide endogenous or exogenous to a prokaryotic or eukaryotic cell, or in vitro. For example, the target sequence can be a polynucleotide residing in the nucleus of the eukaryotic cell. A target sequence can be a sequence coding a gene product (e.g., a protein) or a non-coding sequence (e.g., a regulatory polynucleotide or a junk DNA). It is contemplated herein that the target sequence should be associated with a PAM; that is, a short sequence recognized by a targetable nuclease complex. The precise sequence and length requirements for a PAM differ depending on the nucleic acid-guided nuclease used, but PAMs can be a 2-5 base pair sequences adjacent the target sequence. Examples of PAM sequences are given in the examples section below, and the skilled person will be able to identify further PAM sequences for use with a given nucleic acid-guided nuclease. Further, engineering of the PAM Interacting (PI) domain may allow programming of PAM specificity, improve target site recognition fidelity, and increase the versatility of a nucleic acid-guided nuclease genome engineering platform. Nucleic acid-guided nucleases may be engineered to alter their PAM specificity, for example as described in Kleinstiver et al., Nature. 2015 Jul. 23; 523 (7561): 481-5, the disclosure of which is incorporated herein in its entirety.

A PAM site is a nucleotide sequence in proximity to a target sequence. In most cases, a nucleic acid-guided nuclease can only cleave a target sequence if an appropriate PAM is present. PAMs are nucleic acid-guided nuclease-specific and can be different between two different nucleic acid-guided nucleases. A PAM can be 5′ or 3′ of a target sequence. A PAM can be upstream or downstream of a target sequence. A PAM can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more nucleotides in length. Often, a PAM is between 2-6 nucleotides in length.

In some embodiments disclosed herein, a PAM can be provided on a separate oligonucleotide. In such cases, providing PAM on a oligonucleotide allows cleavage of a target sequence that otherwise would not be able to be cleave because no adjacent PAM is present on the same polynucleotide as the target sequence.

Polynucleotide sequences encoding a component of a targetable nuclease system can include one or more vectors. In general, the term “vector” as used herein can refer to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. Vectors include, but are not limited to, nucleic acid molecules that are single-stranded, double-stranded, or partially double-stranded; nucleic acid molecules that comprise one or more free ends, no free ends (e.g. circular); nucleic acid molecules that comprise DNA, RNA, or both; and other varieties of polynucleotides known in the art. One type of vector is a “plasmid,” which refers to a circular double stranded DNA loop into which additional DNA segments can be inserted, such as by standard molecular cloning techniques. Another type of vector is a viral vector, wherein virally-derived DNA or RNA sequences are present in the vector for packaging into a virus (e.g. retroviruses, replication defective retroviruses, adenoviruses, replication defective adenoviruses, and adeno-associated viruses). Other vectors (e.g., non-episomal mammalian vectors) can be integrated into the genome of a host cell upon introduction into the host cell. Recombinant expression vectors can include a nucleic acid of the invention in a form suitable for expression of the nucleic acid in a host cell, can mean that the recombinant expression vectors include one or more regulatory elements, which may be selected on the basis of the host cells to be used for expression, that is operatively-linked to the nucleic acid sequence to be expressed.

In some embodiments, a regulatory element can be operably linked to one or more elements of a targetable nuclease system so as to drive expression of the one or more components of the targetable nuclease system.

In some embodiments, a vector can include a regulatory element operably linked to a polynucleotide sequence encoding a nucleic acid-guided nuclease. The polynucleotide sequence encoding the nucleic acid-guided nuclease can be codon optimized for expression in targeted cells, such as prokaryotic or eukaryotic cells. Eukaryotic cells can be yeast, fungi, algae, plant, animal, or human cells. Eukaryotic cells can be those derived from an organism, such as a mammal, including but not limited to human, mouse, rat, rabbit, dog, or non-human mammal including non-human primate.

In general, codon optimization can refer to a process of modifying a nucleic acid sequence for enhanced expression in the host cells of interest by replacing at least one codon or more of the native sequence with codons that are more frequently or most frequently used in the genes of that host cell while maintaining the native amino acid sequence. Various species exhibit certain bias for codons of a certain amino acid. As contemplated herein, genes can be tailored for optimal gene expression in a given organism based on codon optimization. Codon usage tables are readily available, for example, at the “Codon Usage Database” available at www.kazusa.orjp and these tables can be adapted in a number of ways. See Nakamura, Y., et al. “Codon usage tabulated from the international DNA sequence databases: status for the year 2000” Nucl. Acids Res. 28:292 (2000).

A nucleic acid-guided nuclease and one or more guide nucleic acids can be delivered either as DNA or RNA. Delivery of a nucleic acid-guided nuclease and guide nucleic acid both as RNA (unmodified or containing base or backbone modifications) molecules can be used to reduce the amount of time that the nucleic acid-guided nuclease persists in the cell. This may reduce the level of off-target cleavage activity in the target cell. Since a nucleic acid-guided nuclease as mRNA takes time to be translated into protein, it can be advantageous to deliver the guide nucleic acid several hours following the delivery of the nucleic acid-guided nuclease mRNA, to maximize the level of guide nucleic acid available for interaction with the nucleic acid-guided nuclease protein. In other cases, the nucleic acid-guided nuclease mRNA and guide nucleic acid are delivered concomitantly. In other examples, the guide nucleic acid is delivered sequentially, such as 0.5, 1, 2, 3, 4, or more hours after the nucleic acid-guided nuclease mRNA.

Guide nucleic acid in the form of RNA or encoded on a DNA expression cassette can be introduced into a host cell can include a nucleic acid-guided nuclease encoded on a vector or chromosome. The guide nucleic acid may be provided in the cassette one or more polynucleotides, which may be contiguous or non-contiguous in the cassette. In specific embodiments, the guide nucleic acid is provided in the cassette as a single contiguous polynucleotide.

A variety of delivery systems can be used to introduce a nucleic acid-guided nuclease (DNA or RNA) and guide nucleic acid (DNA or RNA) into a host cell. In accordance with these embodiments, systems of use can include, but are not limited to, yeast systems, lipofection systems, microinjection systems, biolistic systems, virosomes, liposomes, immunoliposomes, polycations, lipid:nucleic acid conjugates, virions, artificial virions, viral vectors, electroporation, cell permeable peptides, nanoparticles, nanowires (Shalek et al., Nano Letters, 2012), exosomes. Molecular trojan horses liposomes (Pardridge et al., Cold Spring Harb Protoc; 2010; doi:10.1101/pdb.prot5407) may be used to deliver an engineered nuclease and guide nuclease across the blood brain barrier.

In some embodiments, an editing template, also referred to herein as a donor template, is also provided. An editing template may be a component of a vector as described herein, contained in a separate vector, or provided as a separate polynucleotide, such as an oligonucleotide, linear polynucleotide, or synthetic polynucleotide. In some cases, an editing template is on the same polynucleotide as a guide nucleic acid. In some embodiments, an editing template is designed to serve as a template in homologous recombination, such as within or near a target sequence nicked or cleaved by a nucleic acid-guided nuclease as a part of a complex as disclosed herein. An editing template polynucleotide can be of any suitable length, such as about or more than about 10, 15, 20, 25, 50, 75, 100, 150, 200, 500, 1000, or more nucleotides in length. In some embodiments, the editing template polynucleotide is complementary to a portion of a polynucleotide can include the target sequence. When optimally aligned, an editing template polynucleotide might overlap with one or more nucleotides of a target sequences (e.g. about or more than about 1, 5, 10, 15, 20, 25, 30, 35, 40, or more nucleotides). In some embodiments, when a editing template sequence and a polynucleotide can include a target sequence are optimally aligned, the nearest nucleotide of the template polynucleotide is within about 1, 5, 10, 15, 20, 25, 50, 75, 100, 200, 300, 400, 500, 1000, 5000, 10000, or more nucleotides from the target sequence.

In some embodiments, methods are provided for delivering one or more polynucleotides, such as or one or more vectors or linear polynucleotides as described herein, one or more transcripts thereof, and/or one or proteins transcribed therefrom, to a host cell. In some aspects, the invention further provides cells produced by such methods, and organisms can include or produced from such cells. In some embodiments, an engineered nuclease in combination with (and optionally complexed with) a guide nucleic acid is delivered to a cell.

Conventional viral and non-viral based gene transfer methods can be used to introduce nucleic acids in cells, such as prokaryotic cells, eukaryotic cells, mammalian cells, or target tissues. Such methods can be used to administer nucleic acids encoding components of an engineered nucleic acid-guided nuclease system to cells in culture, or in a host organism. Non-viral vector delivery systems include DNA plasmids, RNA (e.g. a transcript of a vector described herein), naked nucleic acid, and nucleic acid complexed with a delivery vehicle, such as a liposome. Viral vector delivery systems include DNA and RNA viruses, which have either episomal or integrated genomes after delivery to the cell. Any gene therapy method known in the art is contemplated of use herein. Methods of non-viral delivery of nucleic acids include are contemplated herein. Adeno-associated virus (“AAV”) vectors may also be used to transduce cells with target nucleic acids, e.g., in the in vitro production of nucleic acids and peptides, and for in vivo and ex vivo gene therapy procedures.

In some embodiments, a host cell is transiently or non-transiently transfected with one or more vectors, linear polynucleotides, polypeptides, nucleic acid-protein complexes, or any combination thereof as described herein. In some embodiments, a cell in transfected in vitro, in culture, or ex vivo. In some embodiments, a cell is transfected as it naturally occurs in a subject. In some embodiments, a cell that is transfected is taken from a subject. In some embodiments, the cell is derived from cells taken from a subject, such as a cell line.

In some embodiments, a cell transfected with one or more vectors, linear polynucleotides, polypeptides, nucleic acid-protein complexes, or any combination thereof as described herein is used to establish a new cell line can include one or more transfection-derived sequences. In some embodiments, a cell transiently transfected with the components of an engineered nucleic acid-guided nuclease system as described herein (such as by transient transfection of one or more vectors, or transfection with RNA), and modified through the activity of an engineered nuclease complex, is used to establish a new cell line can include cells containing the modification but lacking any other exogenous sequence.

In some embodiments, one or more vectors described herein are used to produce a non-human transgenic cell, organism, animal, or plant. In some embodiments, the transgenic animal is a mammal, such as a mouse, rat, or rabbit. Methods for producing transgenic cells, organisms, plants, and animals are known in the art, and generally begin with a method of cell transformation or transfection, such as described herein.

In certain embodiments, an engineered nuclease complex, “target sequence” can refer to a sequence to which a guide sequence is designed to have complementarity, where hybridization between a target sequence and a guide sequence promotes the formation of an engineered nuclease complex. A target sequence can include any polynucleotide, such as DNA, RNA, or a DNA-RNA hybrid. A target sequence can be located in the nucleus or cytoplasm of a cell. A target sequence can be located in vitro or in a cell-free environment.

In some embodiments, formation of an engineered nuclease complex can include a guide nucleic acid hybridized to a target sequence and complexed with one or more novel engineered nucleases as disclosed herein renders cleavage of one or both strands in or near (e.g. within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, or more base pairs from) the targeted sequence. Cleavage can occur within a target sequence, 5′ of the target sequence, upstream of a target sequence, 3′ of the target sequence, or downstream of a target sequence.

In some embodiments, one or more vectors driving expression of one or more components of a targetable nuclease system are introduced into a host cell or in vitro such formation of a targetable nuclease complex at one or more target sites. For example, a nucleic acid-guided nuclease and a guide nucleic acid can each be operably linked to separate regulatory elements on separate vectors. Alternatively, two or more of the elements expressed from the same or different regulatory elements, can be combined in a single vector, with one or more additional vectors providing any components of the targetable nuclease system not included in the first vector. Targetable nuclease system elements that are combined in a single vector may be arranged in any suitable orientation, such as one element located 5′ with respect to (“upstream” of) or 3′ with respect to (“downstream” of) a second element. The coding sequence of one element may be located on the same or opposite strand of the coding sequence of a second element, and oriented in the same or opposite direction. In some embodiments, a single promoter drives expression of a transcript encoding a nucleic acid-guided nuclease and one or more guide nucleic acids. In some embodiments, a nucleic acid-guided nuclease and one or more guide nucleic acids are operably linked to and expressed from the same promoter. In other embodiments, one or more guide nucleic acids or polynucleotides encoding the one or more guide nucleic acids are introduced into a cell or in vitro environment already can include a nucleic acid-guided nuclease or polynucleotide sequence encoding the nucleic acid-guided nuclease.

In some embodiments, when multiple different guide sequences are used, a single expression construct may be used to target nuclease activity to multiple different, corresponding target sequences within a cell or in vitro. For example, a single vector can include about or more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or more guide sequences. In other embodiments, about or more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more such guide-sequence-containing vectors can be provided, and optionally, delivered to a cell in vivo or in vitro.

In some embodiments, methods and compositions disclosed herein can include more than one guide nucleic acid, such that each guide nucleic acid has a different guide sequence, thereby targeting a different target sequence. In accordance with these embodiments, multiple guide nucleic acids can be using in multiplexing, wherein multiple targets are targeted simultaneously. Additionally or alternatively, the multiple guide nucleic acids are introduced into a population of cells, such that each cell in a population received a different or random guide nucleic acid, thereby targeting multiple different target sequences across a population of cells. In such cases, the collection of subsequently altered cells can be referred to as a library.

In other embodiments, methods and compositions disclosed herein can include multiple different nucleic acid-guided nucleases, each with one or more different corresponding guide nucleic acids, thereby allowing targeting of different target sequences by different nucleic acid-guided nucleases. In some such cases, each nucleic acid-guided nuclease can correspond to a distinct plurality of guide nucleic acids, allowing two or more non-overlapping, partially overlapping, or completely overlapping multiplexing events.

In some embodiments, the nucleic acid-guided nuclease has DNA cleavage activity or RNA cleavage activity. In some embodiments, the nucleic acid-guided nuclease directs cleavage of one or both strands at the location of a target sequence, such as within the target sequence and/or within the complement of the target sequence. In some embodiments, the nucleic acid-guided nuclease directs cleavage of one or both strands within about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 50, 100, 200, 500, or more base pairs from the first or last nucleotide of a target sequence.

In certain embodiments, the invention provides for methods of modifying a target sequence in vitro, or in a prokaryotic or eukaryotic cell, which can be in vivo, ex vivo, or in vitro. In some embodiments, the method includes sampling a cell or population of cells such as prokaryotic cells, or those from a human or non-human animal or plant (including micro-algae or other organism), and modifying the cell or cells. Culturing may occur at any stage in vitro or ex vivo. The cell or cells may even be re-introduced into the host, such as a non-human animal or plant (including micro-algae). For re-introduced cells, they can be stem cells.

In some embodiments, the method includes allowing a targetable nuclease complex to bind to the target sequence to effect cleavage of the target sequence, thereby modifying the target sequence, wherein the targetable nuclease complex includes a nucleic acid-guided nuclease complexed with a guide nucleic acid wherein the guide sequence of the guide nucleic acid is hybridized to a target sequence within a target polynucleotide. In some aspects, the invention provides a method of modifying expression of a target polynucleotide in in vitro or in a prokaryotic or eukaryotic cell. In some embodiments, the method includes allowing an targetable nuclease complex to bind to a target sequence with the target polynucleotide such that the binding can lead to in increased or decreased expression of the target polynucleotide; wherein the targetable nuclease complex includes an nucleic acid-guided nuclease complexed with a guide nucleic acid, and wherein the guide sequence of the guide nucleic acid is hybridized to a target sequence within the target polynucleotide.

In certain embodiments, the invention provides kits containing any one or more of the elements disclosed in the above methods and compositions. Elements may provide individually or in combinations, and may be provided in any suitable container, such as a vial, a bottle, or a tube. In some embodiments, the kit includes instructions in one or more languages, for example in more than one language.

In some embodiments, a kit comprises one or more reagents for use in a process utilizing one or more of the elements described herein. Reagents may be provided in any suitable container. For example, a kit may provide one or more reaction or storage buffers. Reagents can be provided in a form that is usable in an assay, or in a form that requires addition of one or more other components before use (e.g. in concentrate or lyophilized form). A buffer can be any buffer, including but not limited to a sodium carbonate buffer, a sodium bicarbonate buffer, a borate buffer, a Tris buffer, a MOPS buffer, a HEPES buffer, and combinations thereof. In some embodiments, the buffer is alkaline. In some embodiments, the buffer has a pH from about 7 to about 10. In some embodiments, the kit includes one or more oligonucleotides corresponding to a guide sequence for insertion into a vector so as to operably link the guide sequence and a regulatory element. In some embodiments, the kit includes a editing template.

In some embodiments, a targetable nuclease complex has a wide variety of utility including modifying (e.g., deleting, inserting, translocating, inactivating, activating) a target sequence in a multiplicity of cell types. As such a targetable nuclease complex of the invention has a broad spectrum of applications in, e.g., biochemical pathway optimization, genome-wide studies, genome engineering, gene therapy, drug screening, disease diagnosis, and prognosis. An exemplary targetable nuclease complex includes a nucleic acid-guided nuclease as disclosed herein complexed with a guide nucleic acid, wherein the guide sequence of the guide nucleic acid can hybridize to a target sequence within the target polynucleotide. A guide nucleic acid can include a guide sequence linked to a scaffold sequence. A scaffold sequence can include one or more sequence regions with a degree of complementarity such that together they form a secondary structure.

An editing template polynucleotide can include a sequence to be integrated (e.g., a mutated gene). A sequence for integration may be a sequence endogenous or exogenous to the cell. Examples of a sequence to be integrated include polynucleotides encoding a protein or a non-coding RNA (e.g., a microRNA). Thus, the sequence for integration may be operably linked to an appropriate control sequence or sequences. Alternatively, the sequence to be integrated may provide a regulatory function. Sequence to be integrated may be a mutated or variant of an endogenous wild-type sequence. Alternatively, sequence to be integrated may be a wild-type version of an endogenous mutated sequence. Additionally or alternatively, sequenced to be integrated may be a variant or mutated form of an endogenous mutated or variant sequence.

In certain embodiments, an upstream or downstream sequence can include from about 20 bp to about 2500 bp, for example, about 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, or about 2500 bp. In some embodiments, an exemplary upstream or downstream sequence has about 15 bp to about 2000 bp, about 30 bp to about 1000 bp, about 50 bp to about 750 bp, about 600 bp to about 1000 bp, or about 700 bp to about 1000 bp.

In some embodiments, the editing template polynucleotide can further include a marker. In certain embodiments, some markers can facilitate screening for targeted integrations. Examples of suitable markers can include, but are not limited to, restriction sites, fluorescent proteins, or selectable markers. In certain embodiments, an exogenous polynucleotide template can be constructed using recombinant techniques.

In one embodiment, an exemplary method for modifying a target polynucleotide by integrating an editing template polynucleotide, a double stranded break is introduced into the genome sequence by an engineered nuclease complex, the break can be repaired via homologous recombination using an editing template such that the template is integrated into the target polynucleotide. The presence of a double-stranded break can increase the efficiency of integration of the editing template.

Disclosed herein are methods for modifying expression of a polynucleotide in a cell. Some methods include increasing or decreasing expression of a target polynucleotide by using a targetable nuclease complex that binds to the target polynucleotide.

Detection of the gene expression level can be conducted in real time in an amplification assay. In one aspect, the amplified products can be directly visualized with fluorescent DNA-binding agents including but not limited to DNA intercalators and DNA groove binders. Because the amount of the intercalators incorporated into the double-stranded DNA molecules can be proportional to the amount of the amplified DNA products, one can conveniently determine the amount of the amplified products by quantifying the fluorescence of the intercalated dye using conventional optical systems in the art. DNA-binding dye suitable for this application include, but are not limited to, SYBR green, SYBR blue, DAPI, propidium iodine, Hoeste, SYBR gold, ethidium bromide, acridines, proflavine, acridine orange, acriflavine, fluorcoumanin, ellipticine, daunomycin, chloroquine, distamycin D, chromomycin, homidium, mithramycin, ruthenium polypyridyls, anthramycin, and others known by one of skill in the art.

In some embodiments, other fluorescent labels such as sequence specific probes can be employed in the amplification reaction to facilitate the detection and quantification of the amplified products. Probe-based quantitative amplification relies on the sequence-specific detection of a desired amplified product. It utilizes fluorescent, target-specific probes (e.g., TaqMan™ probes) resulting in increased specificity and sensitivity. Methods for performing probe-based quantitative amplification are well established in the art.

In some embodiments, an agent-induced change in expression of sequences associated with a signaling biochemical pathway can also be determined by examining the corresponding gene products. Determining the protein level can involve a) contacting the protein contained in a biological sample with an agent that specifically bind to a protein associated with a signaling biochemical pathway; and (b) identifying any agent:protein complex so formed. In one aspect of this embodiment, the agent that specifically binds a protein associated with a signaling biochemical pathway is an antibody, preferably a monoclonal antibody.

In some embodiments, the amount of agent:polypeptide complexes formed during the binding reaction can be quantified by standard quantitative assays. As illustrated above, the formation of agent:polypeptide complex can be measured directly by the amount of label remained at the site of binding. In an alternative, the protein associated with a signaling biochemical pathway is tested for its ability to compete with a labeled analog for binding sites on the specific agent. In this competitive assay, the amount of label captured is inversely proportional to the amount of protein sequences associated with a signaling biochemical pathway present in a test sample.

In some embodiments, a number of techniques for protein analysis based on the general principles outlined above are known in the art and contemplated herein. They include but are not limited to radioimmunoassays, ELISA (enzyme linked immunoradiometric assays), “sandwich” immunoassays, immunoradiometric assays, in situ immunoassays (using e.g., colloidal gold, enzyme or radioisotope labels), western blot analysis, immunoprecipitation assays, immunofluorescent assays, and SDS-PAGE.

In some embodiments, in practicing a subject method, it may be desirable to discern the expression pattern of a protein associated with a signaling biochemical pathway in different bodily tissue, in different cell types, and/or in different subcellular structures. These studies can be performed with the use of tissue-specific, cell-specific or subcellular structure specific antibodies capable of binding to protein markers that are preferentially expressed in certain tissues, cell types, or subcellular structures.

In other embodiment, an altered expression of a gene associated with a signaling biochemical pathway can also be determined by examining a change in activity of the gene product relative to a control cell. The assay for an agent-induced change in the activity of a protein associated with a signaling biochemical pathway will dependent on the biological activity and/or the signal transduction pathway that is under investigation. For example, where the protein is a kinase, a change in its ability to phosphorylate the downstream substrate(s) can be determined by a variety of assays known in the art. Representative assays include but are not limited to immunoblotting and immunoprecipitation with antibodies such as anti-phosphotyrosine antibodies that recognize phosphorylated proteins. In addition, kinase activity can be detected by high throughput chemiluminescent assays.

In certain embodiments, where the protein associated with a signaling biochemical pathway is part of a signaling cascade leading to a fluctuation of intracellular pH condition, pH sensitive molecules such as fluorescent pH dyes can be used as the reporter molecules. In another example where the protein associated with a signaling biochemical pathway is an ion channel, fluctuations in membrane potential and/or intracellular ion concentration can be monitored. A number of commercial kits and high-throughput devices are suited for a rapid and robust screening for modulators of ion channels. Representative instruments include FLIPR™ (Molecular Devices, Inc.) and VIPR (Aurora Biosciences). These instruments are capable of detecting reactions in over 1000 sample wells of a microplate simultaneously, and providing real-time measurement and functional data within a second or even a millisecond.

In practicing any of the methods disclosed herein, a suitable vector can be introduced to a cell, tissue, organism, or an embryo via one or more methods known in the art, including without limitation, microinjection, electroporation, sonoporation, biolistics, calcium phosphate-mediated transfection, cationic transfection, liposome transfection, dendrimer transfection, heat shock transfection, nucleofection transfection, magnetofection, lipofection, impalefection, optical transfection, proprietary agent-enhanced uptake of nucleic acids, and delivery via liposomes, immunoliposomes, virosomes, or artificial virions. In some methods, the vector is introduced into an embryo by microinjection. The vector or vectors may be microinjected into the nucleus or the cytoplasm of the embryo. In some methods, the vector or vectors may be introduced into a cell by nucleofection.

A target polynucleotide of a targetable nuclease complex can be any polynucleotide endogenous or exogenous to the host cell. For example, the target polynucleotide can be a polynucleotide residing in the nucleus of the eukaryotic cell, the genome of a prokaryotic cell, or an extrachromosomal vector of a host cell. The target polynucleotide can be a sequence coding a gene product (e.g., a protein) or a non-coding sequence (e.g., a regulatory polynucleotide or a junk DNA).

Some embodiments disclosed herein relate to use of an engineered nucleic acid guided nuclease system disclosed herein; for example, in order to target and knock out genes, amplify genes and/or repair certain mutations associated with DNA repeat instability and a medical disorder. This nuclease system may be used to harness and to correct these defects of genomic instability. In other embodiments, engineered nucleic acid guided nuclease systems disclosed herein can be used for correcting defects in the genes associated with Lafora disease. Lafora disease is an autosomal recessive condition which is characterized by progressive myoclonus epilepsy which may start as epileptic seizures in adolescence. This condition causes seizures, muscle spasms, difficulty walking, dementia, and eventually death.

In yet another aspect of the invention, the engineered/novel nucleic acid guided nuclease system can be used to correct genetic-eye disorders that arise from several genetic mutations

In certain embodiments disclosed herein engineered nucleic acid guided nuclease constructs can recognize a protospacer adjacent motif (PAM) sequence other than TTTN or in addition to TTTN. In other embodiments, engineered nucleic acid guided nuclease constructs disclosed herein can be further mutated to improve targeting efficiency or can be selected from a library for certain targeted features. Other embodiments disclosed herein concern vectors including constructs disclosed herein of use for further analysis and to select for improved genome editing features.

Other embodiments disclosed herein include kits for packaging and transporting nucleic acid guided nuclease constructs and/or novel gRNAs disclosed herein or known gRNAs disclosed herein and further include at least one container. In certain embodiments, several reagents required for the kits can be included for convenience and ease of transport and efficiency.

EXAMPLES Example 1: Culture of Jurkat Human T-Cell Leukemia Cell Line and Primary Human T-Cells

Human Jurkat T-cell leukemia cells (Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures GmbH (ACC 282)) were propagated in RPMI 1640 medium (ThermoFisher Scientific) with 10% heat-inactivated fetal bovine serum (FBS) (ThermoFisher Scientific) supplemented with 1% penicillin-streptomycin antibiotic mix (ThermoFisher Scientific). Cells were cultured at 37° C. in 5% CO2 incubators and maintained at a density of 0.5 to 1.5×10⁶ cells mL⁻¹. 24 hours before transfection, cells were passaged at 0.1×10⁶ cell mL⁻¹. Cell culture media supernatant was periodically tested for mycoplasma contamination using the MycoAlert PLUS mycoplasma detection kit (Lonza).

Example 2: Primary T-Cell Isolation and Culture

T-cells were isolated from human peripheral blood obtained from healthy adults by immune-magnetic negative selection using the EasySep Human T-cell Isolation Kit (STEMCELL Technologies). After isolation, T-cells were activated in 25 μL mL⁻¹ ImmunoCult Human CD3/CD28/CD2 T-Cell Activator (STEMCELL Technologies) in ImmunoCult-XF T-Cell Expansion Medium (STEMCELL Technologies) containing 12.5 ng mL⁻¹ Human Recombinant IL-2, 5 ng mL⁻¹ IL-7, and 5 ng mL⁻¹ IL-15 (STEMCELL Technologies) and seeded at 1.0×10⁶ cells mL⁻¹. Until transfection 48 hours later, the cells were cultured at 37° C. in 5% CO2 incubators.

Example 3: RNP Formulation

Ribonucleoprotein complexes (RNPs) were generated by incubating respective guide nucleic acids (gNAs) with MAD7 in the molar ratio of 3:2 gNA:MAD7 for 15 minutes at room temperature immediately before transfection. For Jurkat experiments, the RNP complexes were generated by mixing the respective gNA (150 pmol), MAD7 (100 pmol), and nuclease-free water, unless otherwise stated. For T-cell experiments, 1.6 μL of an aqueous solution of 15-50 kDa poly-L-glutamic acid (PGA, 100 μg Alamanda Polymers) was added to gNAs, followed by the addition of MAD7 and nuclease-free water.

Example 4: Generation of Donor Templates Via PCT Amplification

Donor templates comprising site-specific homology arms, respective promoter, and respective gene (GFP or Hu19 scFv-CD8α-CD28-CD3ζ CAR) were amplified from corresponding pTwist Ampicillin high-copy plasmids (Twist Bioscience) using homology arms-specific PCR primers. Donor templates were amplified in a two-step PCR program: initial denaturation at 98° C. for 30 seconds, cycle denaturation at 98° C. for 10 seconds, extension at 72° C. for 30 seconds per kb amplicon for 40-cycles with a hold at 72° C. for 10 minutes. Each 50 PCR reaction contained 10 ng amplification template (plasmid DNA), 0.5 μM homology arm-specific forward and reverse primers, nuclease-free water (IDT), 3% DMSO, and 1× Phusion High-Fidelity PCR Master Mix with HF Buffer (ThermoFisher Scientific). PCR products were purified using NucleoSpin Gel and PCR Clean-up Kit (Macherey-Nagel) with two 20 μL elutions. Purified HDR templates were collected and quantified on NanoDrop One Microvolume UV-Vis Spectrophotometer (ThermoFisher Scientific). Templates were concentrated using Amicon Ultra 0.5 mL 30K Centrifugal Filters: 100 μg DNA per unit was transferred, filled with nuclease-free water to 500 μL, and centrifuged at 10,000 g for 10 minutes to reduce volume to 50 μL. DNA was washed twice with nuclease-free water and recovered into a fresh tube by inversion and centrifugation at 10,000 g for 15 seconds. HDR templates were collected, diluted, and concentrations quantified using Qubit dsDNA HS Assay Kit (ThermoFisher Scientific). HDR templates of 0.5 to 1 μg μL⁻¹ were used for cellular studies.

Example 5: Jurkat Cell Transfection

Lonza 4D Nucleofector with Shuttle unit (V4SC-2960 Nucleocuvette Strips) was used for transfection, following the manufacturer's instructions. For transfection, cells were harvested by centrifugation (200 g, RT, 5 minutes) and re-suspended in 20 μL at 10×10⁶ cells mL⁻¹ in the SF Cell Line Nucleofector X Kit buffer (Lonza), unless stated otherwise. The cell suspension was mixed with the RNPs, immediately transferred to the nucleocuvette, and transfected. After transfection, the cells were immediately re-suspended in the pre-warmed cultivation medium and plated onto 96-well, flat-bottom, non-cell culture treated plates (Falcon), and cultured at 37° C. in 5% CO₂ incubators and maintained at a density of 0.5 to 1.0×10⁶ cells mL⁻¹. After 48 hours, the cells were harvested for the viability assay and genomic DNA, as described below. For the Homology-Directed Repair Template insertion, the HDR template was added to the cells and the suspension transferred to the RNPs immediately before transfection. The transfection parameters, cell recovery step, and proliferation conditions as described in Example 1. The cells were harvested 48 hours post-transfection for the viability assessment, after 7 days for CAR insertion efficiency, or after 7 days, 14 days, and 21 days for GFP insertion efficiency.

Example 6: Primary T-Cell Transfection

48 hours after isolation, the cells were harvested by centrifugation (300 g, RT, 5 minutes) and re-suspended in 20 μL at 50×10⁶ cells mL⁻¹ in the supplemented P3 Primary Cell Nucleofector Kit buffer (Lonza). The cells were mixed with HDR templates and the suspension transferred to the RNPs immediately before transfection (Nucleofection program EH-115). After transfection, 80 μL of pre-warmed cultivation medium without IL-2 was added to the electroporation cuvettes. When using M3814 (Selleckchem), 80 μL of pre-warmed cultivation medium containing 2 μM M3814 final concentration without IL-2 was added to the electroporation cuvettes. After 10 minutes of incubation at 37° C., T-cells were transferred onto 96-well, flat-bottom, non-cell culture treated plates (Falcon) containing pre-warmed cultivation medium pretreated with 2 μM M3814 final concentration and 12.5 ng mL⁻¹ IL-2. The cells were seeded at a density of 0.25×10⁶ cells mL⁻¹, or 1.3×10⁶ cells mL⁻¹ in the experiment with M3814, and kept at 37° C. in 5% CO₂ incubators. The viability assay was carried out 24 hours post-transfection after which the cells were reseeded in the fresh cultivation medium containing IL-2. Insertion efficiency of CAR was measured after 7 days, and 11 days or 13 days post-transfection.

Example 7: Flow Cytometry

Flow cytometric assessments were carried out on a CytoFLEX S instrument (Beckmen Coulter) using a 96-well plate format. Measurements of cell viability, PDCD1 expression, GFP expression, and CAR expression were performed on 10,000 or 20,000 single cell events in Jurkat or primary T-cells, respectively.

For the cell viability and GFP knock-in measurements, approximately 250,000 cells per sample were transferred onto 96-well V-bottom cell culture plates and assessed following a series of consecutive washing and staining steps. The first step included centrifuging the cells at 300 g for 5 minutes at room temperature, discarding the supernatant, and washing cells in 150 μL Dulbecco's PBS/2% FBS (STEMCELL Technologies) or Cell Staining Buffer (Biolegend), respectively, followed by the second centrifugation and removal of supernatant. The final step included viability staining of cells using 150 μL Dulbecco's PBS/2% FBS with 7-amino-actinomycin D (7-AAD, 1:1,000; ThermoFisher) or 50 μL Cell Staining Buffer with Zombie Violet Dye (1:200; Biolegend), respectively. The measurements of cell viability and GFP expression were collected simultaneously for 7-AAD (excitation: yellow-green laser; emission: 561 nm), Zombie Violet (excitation: violet laser; emission 405 nm), and GFP (excitation: blue laser; emission 488 nm) as needed.

For detection of CAR knock-in efficiency, approx. 250,000 cells per sample were transferred onto 96-well V-bottom, washed as described above using Cell Staining Buffer, and re-suspended in 50 μL Cell Staining Buffer with PE Anti-Myc tag antibody [9E10] (1:50; Abcam) and Zombie Violet Dye (1:200; Biolegend) for 30 minutes. Afterwards, the cells were washed in two subsequent washing steps using 150 μL Cell Staining Buffer, and finally re-suspended in 100 μL Cell Staining Buffer for the flow cytometry measurements (excitation: yellow-green laser; emission: 561 nm).

For detection of PDCD1 knock-out efficiency, approx. 250,000 Jurkat cells per sample were transferred onto 96-well V-bottom cell culture plates and assessed following a series of consecutive washing and staining steps. The first step included centrifuging the cells at 300 g for 5 minutes at 4° C. and discarding the supernatant. Afterwards, the cells were stained using 100 μL Cell Staining Buffer (Biolegend) with APC/Cyanine7 anti-human CD279 (PD-1) antibody (1:100; Biolegend) and incubated for 30 minutes at 4° C. in the dark. The cells were then centrifuged at 300 g for 5 minutes at 4° C. and the supernatant discarded. The next step included two repeats of centrifugation at 300 g for 5 minutes at 4° C., supernatant removal, and cell washing in 150 μL ice-cold Cell Staining Buffer (Biolegend). In the final step, the cells were re-suspended in 100 μL Cell Staining Buffer for the flow cytometry measurements (excitation: red laser; emission: 633 nm).

Example 8: DNA Extraction

Cells were harvested 48-h post-transfection by centrifugation (1,000 g, 10 minutes) in 96-well, V-bottom plates (Greiner), washed with PBS (Sigma Aldrich) and lysed in 20 μL QuickExtract DNA Extraction Solution (Epicentre, Lucigen). DNA was extracted following the manufacturer's protocol: 15 minutes at 65° C., 15 minutes at 68° C., 10 minutes at 95° C., cooled to 4° C., and stored at 4° C. Genomic DNA was diluted 20-fold in nuclease-free water before amplicon PCR reactions.

Example 9: Amplicon Sequencing

Extracted genomic DNA was quantified using the NanoDrop (ThermoFisher Scientific). Amplicons were constructed in two PCR steps: in the first PCR, regions of interest (150-400 bp) were amplified from 10 to 30 ng of genomic DNA with primers containing Illumina forward and reverse adapters on both ends comprising suitable loci-specific complementary sequences, using Phusion High-Fidelity PCR Master Mix (ThermoFisher Scientific). Amplification products were purified with Agencourt AMPure XP beads (Ramcon), using the sample to beads ratio of 1:1.8. The DNA was eluted from the beads with nuclease-free water and the size of the purified amplicons analyzed on a 2% agarose E-gel using the E-gel electrophoresis system (ThermoFisher Scientific). In the second PCR, unique pairs of Illumina-compatible indexes (Nextera XT Index Kit v2) were added to the amplicons using the KAPA HiFi HotStart Ready Mix (Roche). The amplified products were purified with Agencourt AMPure XP beads (Ramcon), using the sample to bead ratio of 1:1.8. The DNA was eluted from the beads with 10 mM Tris-HCl pH 8.5, 0.1% Tween 20. Sizes of the purified DNA fragments were validated on a 2% agarose gel using the E-gel electrophoresis system (ThermoFisher Scientific), quantified using Qubit dsDNA HS Assay Kit (Thermo Fisher) and then pooled in equimolar concentrations. Quality of the amplicon library was validated using Bioanalyzer, High Sensitivity DNA Kit (Agilent) before sequencing. The final library was sequenced on Illumina MiSeq System using the MiSeq Reagent Kit v.2 (300 cycles, 2×250 bp, paired-end reads). De-multiplexed FASTQ files were obtained from BaseSpace (Illumina).

Example 10: NGS Data Analysis

Initial quality assessment of the obtained reads was performed with FastQC36. The sequencing data were aligned and analyzed with the CRISPResso2 software, using CRISPRessoBatch command with the parameters—cleavage_offset 1—quantification_window_size 10—quantification_window_center 1—expand_ambiguous_alignments for the INDEL frequency analysis. For the ORF disruption analysis, CRISPRessoBatch command with the parameters—cleavage_offset 1—coding_seq <EXON_SEQ>—quantification_window_size 0—quantification_window_center 1—expand_ambiguous_alignments was used. Modification rates from the CRISPResso2 software output were analyzed in Excel.

Example 11: CRISPR-MAD7 Platform for Human Genome Editing Using the Jurkat T-Cell Leukemia Line

MAD7 nuclease comprising a His6 tag (SEQ ID NO: 423) and either one (MAD7-1NLS) or four (MAD7-4NLS) nuclear localization signals (NLS) were used (FIG. 1 ). RNPs were generated as described in Example 3. Editing frequency of the MAD7 nuclease complexed with one or more guide nucleic acids comprising a spacer sequence of SEQ ID NOs: 86-384 as shown in Table 1 was determined by nucleofection of RNPs in Jurkat T-cells using the Lonza recommended nucleofection program SE-CL-120 (Example 5), followed by genomic DNA extraction (Example 8), amplification of the edited locus and targeted next-generation sequencing (Example 9) for identification of the edits, and finally by computational analysis (Example 10) of modification frequency using the CRISPResso2 algorithm.

TABLE 1 Spacer sequences Name PAM SEQ ID NO Spacer sequence crCD247_1 TTTC 114 ACCGCGGCCAUCCUGCAGGCA crCD247_2 TTTC 115 UGAGGGAAAGGACAAGAUGAA crCD247_3 TTTG 116 GGAUCCAGCAGGCCAAAGCUC crCD247_4 TTTC 117 CUAGCAGAGAAGGAAGAACCC crCD247_5 TTTC 118 UGUGUUGCAGUUCAGCAGGAG crCD247_6 CTTC 119 CUGAGGGUUCUUCCUUCUCUG crCD247_7 CTTC 120 CCGUUGUCUUUCCUAGCAGAG crCD247_8 TTTC 121 UGCAGUUCCUGCAGAAGAGGG crCD247_9 CTTC 122 UGCAGGAACUGCAGAAAGAUA crCD247_10 TTTC 123 AUCCCAAUCUCACUGUAGGCC crCD247_11 CTTT 124 CAUCCCAAUCUCACUGUAGGC crCD247_12 TTTT 125 CUCAUUUCACUCCCAAACAAC crCD247_13 TTTC 126 UCAUUUCACUCCCAAACAACC crCD247_14 TTTC 127 ACUCCCAAACAACCAGCGCCG crCD247_15 CTTA 128 CGUUAUAGAGCUGGUUCUGGC crCD247_16 TTTG 129 UUUUCUGAUUUGCUUUCACGC crCD247_17 TTTC 130 UGAUUUGCUUUCACGCCAGGG crCD247_18 TTTG 131 CUUUCACGCCAGGGUCUCAGU crCD247_19 TTTC 132 ACGCCAGGGUCUCAGUACAGC crCD247_20 TTTC 133 CGGAGGGUCUACGGCGAGGCU crCD247_21 TTTC 134 UUAUCUGUUAUAGGAGCUCAA crCD247_22 CTTA 135 UCUGUUAUAGGAGCUCAAUCU crCD247_23 CTTG 136 UCCAAAACAUCGUACUCCUCU crCD247_24 TTTC 137 CCCCCAUCUCAGGGUCCCGGC crCD247_25 TTTG 138 GACAAGAGACGUGGCCGGGAC crCD247_26 TTTC 139 UCUCCCUCUAACGUCUUCCCG crCTLA4_1 TTTG 140 CCUGGAGAUGCAUACUCACAC crCTLA4_2 TTTG 141 CAGAAGACAGGGAUGAAGAGA crCTLA4_3 TTTC 142 CACUGGAGGUGCCCGUGCAGA crCTLA4_4 TTTG 143 UGUGUGAGUAUGCAUCUCCAG crCTLA4_5 TTTC 144 AGCGGCACAAGGCUCAGCUGA crCTLA4_6 CTTG 145 UGCCGCUGAAAUCCAAGGCAA crCTLA4_7 CTTT 146 UCCAUGCUAGCAAUGCACGUG crCTLA4_8 TTTT 147 CCAUGCUAGCAAUGCACGUGG crCTLA4_9 CTTT 148 GUGUGUGAGUAUGCAUCUCCA crCTLA4_10 CTTT 149 GCCUGGAGAUGCAUACUCACA crCTLA4_11 CTTC 150 GGCAGGCUGACAGCCAGGUGA crCTLA4_12 CTTC 151 AGUCACCUGGCUGUCAGCCUG crCTLA4_13 CTTC 152 CUAGAUGAUUCCAUCUGCACG crCTLA4_14 CTTG 153 CCUUGGAUUUCAGCGGCACAA crCTLA4_15 CTTG 154 AUUUCCACUGGAGGUGCCCGU crCTLA4_16 CTTG 155 GAUAGUGAGGUUCACUUGAUU crCTLA4_17 CTTG 156 CAGAUGUAGAGUCCCGUGUCC crCTLA4_18 TTTG 157 CUCACCAAUUACAUAAAUCUG crCTLA4_19 CTTT 158 GCUCACCAAUUACAUAAAUCU crCTLA4_20 CTTT 159 GUUUUCUGUUGCAGAUCCAGA crCTLA4_21 TTTG 160 UUUUCUGUUGCAGAUCCAGAA crCTLA4_22 TTTT 161 CUGUUGCAGAUCCAGAACCGU crCTLA4_23 CTTC 162 CUCCUCUGGAUCCUUGCAGCA crCTLA4_24 CTTG 163 CAGCAGUUAGUUCGGGGUUGU crCTLA4_25 CTTG 164 GAUUUCAGCGGCACAAGGCUC crCTLA4_26 TTTT 165 UUUAUAGCUUUCUCCUCACAG crCTLA4_27 CTTT 166 CUCCUCACAGCUGUUUCUUUG crCTLA4_28 TTTC 167 UCCUCACAGCUGUUUCUUUGA crCTLA4_29 TTTT 168 GCUCAAAGAAACAGCUGUGAG crCTLA4_30 TTTC 169 UUUUUGUGUUUGACAGCUAAA crCTLA4_31 TTTT 170 UGUGUUUGACAGCUAAAGAAA crCTLA4_32 TTTG 171 ACAGCUAAAGAAAAGAAGCCC crCTLA4_33 TTTT 172 CACAUAGACCCCUGUUGUAAG crCTLA4_34 TTTT 173 CACAUUCUGGCUCUGUUGGGG crCTLA4_35 CTTT 174 UCACAUUCUGGCUCUGUUGGG crCTLA4_36 TTTC 175 AGCCUUAUUUUAUUCCCAUCA crCTLA4_37 TTTC 176 UCAAUUGAUGGGAAUAAAAUA crCTLA4_38 TTTT 177 UUCUUCUCUUCAUCCCUGUCU crCTLA4_39 CTTT 178 GCAGAAGACAGGGAUGAAGAG crCTLA4_40 CTTT 179 GGCUUUUCCAUGCUAGCAAUG crCTLA4_41 TTTG 180 GCUUUUCCAUGCUAGCAAUGC crLAG3_1 TTTG 181 GGGUGCAUACCUGUCUGGCUG crLAG3_2 TTTG 182 GGUCACCUGGAUCCCUGGGGA crLAG3_3 TTTC 183 UCAGGACCUUGGCUGGAGGCA crLAG3_4 TTTC 184 CCAGCCUUGGCAAUGCCAGCU crLAG3_5 TTTG 185 UGAGGUGACUCCAGUAUCUGG crLAG3_6 CTTG 186 CUGUUUCUGCAGCCGCUUUGG crLAG3_7 CTTG 187 CACAGUGACUGCCAGCCCCCC crLAG3_8 TTTT 188 GAACUGCUCCUUCAGCCGCCC crLAG3_9 CTTC 189 AGCCGCCCUGACCGCCCAGCC crLAG3_10 TTTC 190 CGCUAAGUGGUGAUGGGGGGA crLAG3_11 CTTT 191 CCGCUAAGUGGUGAUGGGGGG crLAG3_12 CTTA 192 GCGGAAAGCUUCCUCUUCCUG crLAG3_13 CTTG 193 GGGCAGGAAGAGGAAGCUUUC crLAG3_14 CTTC 194 CUCUUCCUGCCCCAAGUCAGC crLAG3_15 CTTC 195 AACGUCUCCAUCAUGUAUAAC crLAG3_16 TTTT 196 CUUUUCUCUUCAGGUCUGGAG crLAG3_17 TTTC 197 UGCAGCCGCUUUGGGUGGCUC crLAG3_18 TTTT 198 CUCUUCAGGUCUGGAGCCCCC crLAG3_19 CTTG 199 ACAGUGUACGCUGGAGCAGGU crLAG3_20 CTTG 200 GCAGUGAGGAAAGACCGGGUC crLAG3_21 TTTC 201 CUCACUGCCAAGUGGACUCCU crLAG3_22 CTTT 202 ACCCUUCGACUAGAGGAUGUG crLAG3_23 TTTA 203 CCCUUCGACUAGAGGAUGUGA crLAG3_24 CTTC 204 GACUAGAGGAUGUGAGCCAGG crLAG3_25 TTTC 205 CCACCUGAGGCUGACCUGUGA crLAG3_26 CTTT 206 CCCACCUGAGGCUGACCUGUG crLAG3_27 CTTC 207 UACUCUUUUCAGUGACUCCCA crLAG3_28 TTTT 208 ACCUGGAGCCACCCAAAGCGG crLAG3_29 TTTT 209 CAGUGACUCCCAAAUCCUUUG crLAG3_30 CTTC 210 CCCAGGGAUCCAGGUGACCCA crLAG3_31 CTTT 211 GGGUCACCUGGAUCCCUGGGG crLAG3_32 CTTT 212 GUGAGGUGACUCCAGUAUCUG crLAG3_33 CTTT 213 GUGUGGAGCUCUCUGGACACC crLAG3_34 TTTG 214 UGUGGAGCUCUCUGGACACCC crLAG3_35 CTTG 215 GCUGGAGGCACAGGAGGCCCA crLAG3_36 TTTT 216 GCUCACCUAGUGAAGCCUCUC crLAG3_37 CTTT 217 CCCAGCCUUGGCAAUGCCAGC crLAG3_38 CTTG 218 GCAAUGCCAGCUGUACCAGGG crLAG3_39 CTTC 219 UUGGAGCAGCAGUGUACUUCA crLAG3_40 CTTC 220 ACAGAGCUGUCUAGCCCAGGU crLAG3_41 CTTT 221 CUCCAUAGGUGCCCAACGCUC crLAG3_42 TTTC 222 UCCAUAGGUGCCCAACGCUCU crLAG3_43 TTTC 223 UCAUCCUUGGUGUCCUUUCUC crLAG3_44 CTTG 224 GUGUCCUUUCUCUGCUCCUUU crLAG3_45 CTTT 225 CUCUGCUCCUUUUGGUGACUG crLAG3_46 CTTC 226 UGCGAAGAGCAGGGGUCACUU crLAG3_47 CTTT 227 UGGUGACUGGAGCCUUUGGCU crLAG3_48 TTTT 228 GGUGACUGGAGCCUUUGGCUU crLAG3_49 CTTT 229 GGCUUUCACCUUUGGAGAAGA crLAG3_50 TTTG 230 GCUUUCACCUUUGGAGAAGAC crLAG3_51 CTTG 231 CUCUAAGGCAGAAAAUCGUCU crLAG3_52 TTTT 232 CUGCCUUAGAGCAAGGGAUUC crLAG3_53 CTTA 233 GAGCAAGGGAUUCACCCUCCG crLAG3_54 TTTC 234 CCGCCCAGUGGCCCGCCCGCU crLAG3_55 CTTC 235 UCGCUAUGGCUGCGCCCAGCC crLAG3_56 TTTA 236 UCCUUGCACAGUGACUGCCAG crPDCD1_1 TTTA 237 GCACGAAGCUCUCCGAUGUGU crPDCD1_2 TTTC 238 UCUGCAGGGACAAUAGGAGCC crPDCD1_3 TTTC 239 CAGUGGCGAGAGAAGACCCCG crPDCD1_4 TTTC 240 CUAGCGGAAUGGGCACCUCAU crPDCD1_5 CTTC 241 GUGCUAAACUGGUACCGCAUG crPDCD1_6 CTTC 242 AACCUGACCUGGGACAGUUUC crPDCD1_7 CTTG 243 UCCGUCUGGUUGCUGGGGCUC crPDCD1_8 CTTC 244 CCCGAGGACCGCAGCCAGCCC crPDCD1_9 CTTC 245 CGUGUCACACAACUGCCCAAC crPDCD1_10 CTTC 246 CACAUGAGCGUGGUCAGGGCC crPDCD1_11 CTTT 247 GAUCUGCGCCUUGGGGGCCAG crPDCD1_12 TTTG 248 AUCUGCGCCUUGGGGGCCAGG crPDCD1_13 CTTG 249 GGGGCCAGGGAGAUGGCCCCA crPDCD1_14 CTTT 250 GUGCCCUUCCAGAGAGAAGGG crPDCD1_15 TTTG 251 UGCCCUUCCAGAGAGAAGGGC crPDCD1_16 TTTC 252 CCUUCCGCUCACCUCCGCCUG crPDCD1_17 CTTC 253 CAGAGAGAAGGGCAGAAGUGC crPDCD1_18 CTTC 254 UGCCCUUCUCUCUGGAAGGGC crPDCD1_19 TTTG 255 GAACUGGCCGGCUGGCCUGGG crPDCD1_20 CTTT 256 CUCCUCAAAGAAGGAGGACCC crPDCD1_21 TTTC 257 UCCUCAAAGAAGGAGGACCCC crPDCD1_22 CTTC 258 UCUCGCCACUGGAAAUCCAGC crPDCD1_23 CTTT 259 CCUAGCGGAAUGGGCACCUCA crPDCD1_24 CTTC 260 CGCUCACCUCCGCCUGAGCAG crPDCD1_25 CTTG 261 GCCCCUCUGACCGGCUUCCUU crPDCD1_26 CTTC 262 UCCACUGCUCAGGCGGAGGUG crPDCD1_27 CTTC 263 UCCCCAGCCCUGCUCGUGGUG crPDCD1_28 CTTC 264 GGUCACCACGAGCAGGGCUGG crPDCD1_29 CTTC 265 ACCUGCAGCUUCUCCAACACA crPDCD1_30 CTTC 266 UCCAACACAUCGGAGAGCUUC crPTPN1_1 TTTA 267 CCUGACAGCGAAUCAUAACAU crPTPN1_2 TTTC 268 AUUCCAACUUACCUAACGGAA crPTPN1_3 TTTC 269 UGUGCGCACUGGUGAUGACAA crPTPN11_4 TTTC 270 CAAUCUGCUCACCUGCUUGAG crPTPN11_5 TTTC 271 UUCUAGUUGAUCAUACCAGGG crPTPN11_6 TTTA 272 AUAACUUACCUCAAAUUCUUC crPTPN11_7 CTTA 273 CCUAACGGAAAGUGUGAAGUC crPTPN11_8 TTTC 274 CAGACACUACAACAACAGGAG crPTPN11_9 TTTA 275 GGUGGUUUCAUGGACAUCUCU crPTPN11_10 TTTC 276 CCAGAGAGAUGUCCAUGAAAC crPTPN6_1 TTTC 277 UAUGACCUGUAUGGAGGGGAG crPTPN6_2 TTTG 278 CGACUCUGACAGAGCUGGUGG crPTPN6_3 TTTG 279 CAGAAGCAGGAGGUGAAGAAC crPTPN6_4 TTTG 280 ACUGCCCCCCACCCAGGCCUG crPTPN6_5 CTTA 281 UGGGCCCUACUCUGUGACCAA crPTPN6_6 TTTC 282 ACCGAGACCUCAGUGGGCUGG crPTPN6_7 CTTC 283 UCUAGGUGGUACCAUGGCCAC crPTPN6_8 CTTG 284 GCCUGCAGCAGCGUCUCUGCC crPTPN6_9 TTTC 285 UUGUGCGUGAGAGCCUCAGCC crPTPN6_10 CTTC 286 GUGCUUUCUGUGCUCAGUGAC crPTPN6_11 CTTG 287 GGCUGGUCACUGAGCACAGAA crPTPN6_12 CTTT 288 CUGUGCUCAGUGACCAGCCCA crPTPN6_13 TTTC 289 UGUGCUCAGUGACCAGCCCAA crPTPN6_14 CTTG 290 AUGUGGGUGACCCUGAGCGGG crPTPN6_15 CTTA 291 CCUCGCACAUGACCUUGAUGU crPTPN6_16 TTTG 292 GCUCCCCCCAGGGUGGACGCU crPTPN6_17 CTTG 293 AGCAGGGUCUCUGCAUCCAGC crPTPN6_18 TTTG 294 GAGACCUUCGACAGCCUCACG crPTPN6_19 CTTC 295 GACAGCCUCACGGACCUGGUG crPTPN6_20 TTTC 296 AAGAAGACGGGGAUUGAGGAG crPTPN6_21 CTTC 297 UUGUUCAGUUCCAACACUCGG crPTPN6_22 CTTG 298 GCUGUAUCCUCGGACUCCUGC crPTPN6_23 TTTC 299 CCCACCCACAUCUCAGAGUUU crPTPN6_24 CTTC 300 CAGACGCUGGUGCAAGUUCUU crPTPN6_25 CTTG 301 CACCAGCGUCUGGAAGGGCAG crPTPN6_26 CTTG 302 UUCUCUGGCCGCUGCCCUUCC crPTPN6_27 CTTG 30 AUGUAGUUGGCAUUGAUGUAG crPTPN6_28 CTTG 304 CGUCCAGAACCAGCUGCUAGG crPTPN6_29 CTTC 305 UGGCAGAUGGCGUGGCAGGAG crPTPN6_30 TTTC 306 UCCACCUCUCGGGUGGUCAUG crPTPN6_31 CTTT 307 CUCCACCUCUCGGGUGGUCAU crPTPN6_32 CTTT 308 CCAGAACAAAUGCGUCCCAUA crPTPN6_33 TTTC 309 CAGAACAAAUGCGUCCCAUAC crPTPN6_34 TTTG 310 UAUUCGGUUGUGUCAUGCUCC crPTPN6_35 CTTA 311 CAGGUCUCCCCGCUGGACAAU crPTPN6_36 CTTC 312 CUGGCUCGGCCCAGUCGCAAG crPTPN6_37 CTTA 313 GGGAGACCUGAUUCGGGAGAU crPTPN6_38 CTTC 314 CUGGACCAGAUCAACCAGCGG crPTPN6_39 TTTC 315 CUGCCGCUGGUUGAUCUGGUC crPTPN6_40 CTTT 316 CCUGCCGCUGGUUGAUCUGGU crPTPN6_41 CTTG 317 GUGGAGAUGUUCUCCAUGAGC crPTPN6_42 CTTG 318 UACUGCGCCUCCGUCUGCACC crPTPN6_43 TTTC 319 AAUGAACUGGGCGAUGGCCAC crPTPN6_44 CTTC 320 UUCUUAGUGGUUUCAAUGAAC crPTPN6_45 CTTC 321 UCCCCUCCAUACAGGUCAUAG crPTPN6_46 CTTG 322 GAGUCUAGUGCAGGGACCGUG crPTPN6_47 CTTG 323 CCCCCCUGCACCCGGCUGCAG crPTPN6_48 CTTG 324 UGUCUGCAGCCGGGUGCAGGG crPTPN6_49 TTTC 325 UCCUCCCUCUUGUUCUUAGUG crPTPN6_50 CTTT 326 CUCCUCCCUCUUGUUCUUAGU crPTPN6_51 CTTC 327 UUCACUUUCUCCUCCCUCUUG crPTPN6_52 CTTG 328 AGGUGGAUGAUGGUGCCGUCG crPTPN6_53 CTTC 329 CCUGACGCUGCCUUCUCUAGG crTIGIT_1 TTTC 330 AGGCCUUACCUGAGGCGAGGG crTIGIT_2 TTTT 331 GUCCUCCCUCUAGUGGCUGAG crTIGIT_3 CTTG 332 GGGUGGCACAUCUCCCCAUCC crTIGIT_4 TTTC 333 UGCAGAGAAAGGUGGCUCUAU crTIGIT_5 TTTG 334 UAAUGCUGACUUGGGGUGGCA crTIGIT_6 CTTA 335 CCUGAGGCGAGGGGAGCCUGC crTIGIT_7 CTTG 336 AAGGAUGGGGAGAUGUGCCAC crTIGIT_8 CTTC 337 AAGGAUCGAGUGGCCCCAGGU crTIGIT_9 CTTC 338 UGCAUCUAUCACACCUACCCU crTIGIT_10 TTTC 339 UAGGACCUCCAGGAAGAUUCU crTIGIT_11 CTTT 340 CUAGGACCUCCAGGAAGAUUC crTIGIT_12 CTTG 341 CUCCAGCAGGAAUACCUGAGC crTIGIT_13 CTTG 342 GAGCCAUGGCCGCGACGCUGG crTIGIT_14 TTTC 343 UAGUCAACGCGACCACCACGA crTIGIT_15 CTTT 344 CUAGUCAACGCGACCACCACG crTIGIT_16 TTTG 345 UAGUUUGUUUGUUUUUAGAAG crTIGIT_17 TTTG 346 UUUGUUUUUAGAAGAAAGCCC crTIGIT_18 TTTG 347 UUUUUAGAAGAAAGCCCUCAG crTIGIT_19 TTTT 348 UAGAAGAAAGCCCUCAGAAUC crTIGIT_20 CTTC 349 CACAGAAUGGAUUCUGAGGGC crTIGIT_21 TTTT 350 CUCCUGAGGUCACCUUCCACA crTIGIT_22 CTTC 351 CUGGGGGUGAGGGAGCACUGG crTIGIT_23 CTTC 352 UGCCUGGACACAGCUUCCUGG crTIGIT_24 CTTC 353 GUCCUCUUCCCUAGGAAUGAU crTIGIT_25 CTTC 354 UGUAACUCAGGACAUUGAAGU crTIGIT_26 CTTC 355 AAUGUCCUGAGUUACAGAAGC crTIGIT_27 TTTC 356 UAUUGUGCCUGUCAUCAUUCC crTIGIT_28 TTTC 357 UCUGCAGAAAUGUUCCCCGUU crTIGIT_29 CTTT 358 CUCUGCAGAAAUGUUCCCCGU crTIGIT_30 CTTG 359 UGCCGUGGUGGAGGAGAGGUG crTIGIT_31 CTTC 360 UGGCCAUUUGUAAUGCUGACU crTIM3_1 CTTA 361 CUUGUAAGUAGUAGCAGCAGC crTIM3_2 TTTC 362 CAAGGAUGCUUACCACCAGGG crTIM3_3 CTTG 363 UAAGUAGUAGCAGCAGCAGCA crTIM3_4 CTTA 364 CCACCAGGGGACAUGGCCCAG crTIM3_5 TTTG 365 AAUGUGGCAACGUGGUGCUCA crTIM3_6 CTTT 366 UCUUCUGCAAGCUCCAUGUUU crTIM3_7 CTTT 367 GCCCCAGCAGACGGGCACGAG crTIM3_8 TTTC 368 AUCAGUCCUGAGCACCACGUU crTIM3_9 CTTT 369 CAUCAGUCCUGAGCACCACGU crTIM3_10 TTTA 370 GCCAGUAUCUGGAUGUCCAAU crTIM3_11 TTTG 371 CGGAAAUCCCCAUUUAGCCAG crTIM3_12 CTTT 372 GCGGAAAUCCCCAUUUAGCCA crTIM3_13 TTTC 373 CGCAAAGGAGAUGUGUCCCUG crTIM3_14 TTTG 374 GAUCCGGCAGCAGUAGAUCCC crTIM3_15 TTTT 375 UCAUCAUUCAUUAUGCCUGGG crTIM3_16 TTTT 376 CUUCUGCAAGCUCCAUGUUUU crTIM3_17 CTTC 377 AGGUUAAAUUUUUCAUCAUUC crTIM3_18 TTTG 378 AUGACCAACUUCAGGUUAAAU crTIM3_19 TTTA 379 ACCUGAAGUUGGUCAUCAAAC crTIM3_20 CTTA 380 UGUUGUUUCUGACAUUAGCCA crTIM3_21 TTTC 381 UGACAUUAGCCAAGGUCACCC crTIM3_22 CTTG 382 GAAAGGCUGCAGUGAAGUCUC crTIM3_23 CTTC 383 ACUGCAGCCUUUCCAAGGAUG crTIM3_24 CTTT 384 CCAAGGAUGCUUACCACCAGG crTIM3_25 TTTT 385 CACAUCUUCCCUUUGACUGUG crTIM3_26 TTTT 386 UAUAGCAGAGACACAGACACU crTIM3_27 TTTA 387 UAUCAGGGAGGCUCCCCAGUG crTIM3_28 CTTA 388 CUGUUAGAUUUAUAUCAGGGA crTIM3_29 TTTG 389 UGUUUCCAUAGCAAAUAUCCA crTIM3_30 TTTC 390 CAUAGCAAAUAUCCACAUUGG crTIM3_31 CTTA 391 CGGGACUCUGGAGCAACCAUC crTIM3_32 TTTG 392 AAAAUUAAAGCGCCGAAGAUA crTIM3_33 CTTA 393 CAUUUGAAAAUUAAAGCGCCG crTIM3_34 CTTT 394 UGUUUCCCCCUUACUAGGGUA crTIM3_35 TTTT 395 GUUUCCCCCUUACUAGGGUAU crTIM3_36 CTTT 396 GACUGUGUCCUGCUGCUGCUG crTIM3_37 TTTC 397 CCCCUUACUAGGGUAUUCUCA crTIM3_38 CTTA 398 CUAGGGUAUUCUCAUAGCAAA crTIM3_39 CTTA 399 AAUUCUGUAUCUUCUCUUUGC crTIM3_40 CTTT 400 AUUUCCACAGCCUCAUCUCUU crTIM3_41 TTTA 401 UUUCCACAGCCUCAUCUCUUU crTIM3_42 TTTC 402 CACAGCCUCAUCUCUUUGGCC crTIM3_43 TTTG 403 GCCAACCUCCCUCCCUCAGGA crTIM3_44 TTTG 404 CCAAUCCUGAGGGAGGGAGGU crTIM3_45 TTTT 405 CUUCUGAGCGAAUUCCCUCUG crTIM3_46 CTTC 406 AUAUACGUUCUCUUCAAUGGU crTIM3_47 CTTT 407 GGGUUGUCGCUUUGCAAUGCC crTIM3_48 TTTG 408 GGUUGUCGCUUUGCAAUGCCA crTIM3_49 CTTC 409 UCUCUCUAUGCAGGGUCCUCA crTIM3_50 CTTC 410 UACACCCCAGCCGCCCCAGGG crTIM3_51 TTTG 411 CCCCAGCAGACGGGCACGAGG crAAVS1 TTTC 412 TTAGGATGGCCTTCTCCGACG

Firstly, using a gNA targeting the DNMT1 locus, the editing frequency of MAD7 comprising either one or four NLS complexed with the respective gNA was compared. RNP concentration-dependent modification efficiency was observed as evidenced by an increased fraction of modified amplicons (FIG. 2 , left axis, dark grey for MAD7-1NLS and light grey representing MAD7-4NLS). Error bars represent one standard deviation for a sample of 3 (n=3). In this experiment, editing frequency was enhanced in Jurkat cells when treated with RNPs comprising MAD-4NLS, which indicates that optimization of the NLS can improve editing efficiency. A slight decrease in cell viability was seen at higher concentrations of RNP for those comprising four NLS as compared to one NLS (FIG. 2 , right axis). Specifically, FIG. 2 shows editing frequency at the DNMT1 locus (n=3; Mean±SD) and cell viability of T-cell leukemic cells as a function of MAD7 comprising one or four nuclear localization signal (NLS) and MAD7-RNP amounts (pmol; constant ratio of 1:1.5 MAD7:gNA). Dark grey bars and circles represent mean modification frequency and viability using MAD7-1NLS, respectively. Light grey bars and triangles represent mean modification frequency and viability using MAD7-4NLS, respectively.

To optimize editing activity, 93 different transfection conditions were tested; 31 nucleofection programs in combination with three buffers—on the Lonza Nucleofector 96-well Shuttle System (FIGS. 3-5 ). FIGS. 3, 4, and 5 show the editing frequency (bars; x-axis) of each of the electroporation conditions (buffers SE, SF, and SG respectively) as compared to a control (y-axis, control at the top). The majority of buffer-program transfection combinations resulted in suboptimal viability (dots; x-axis) and editing frequency, however, the analysis revealed several conditions that supported substantial rates of both cell viability and editing. Two improved conditions observed in the screen, namely SF-CA-137 and SG-CA-138, were then validated and compared to the Lonza recommended nucleofection programs for T-cell leukemia, namely SE-CL-120 and SE-CK-116 (FIG. 6 ). Specifically, FIG. 6 shows editing frequency at the DNMT1 locus (n=4; Mean±SD) in T-cell leukemic cell line achieved by utilization of the transfection conditions identified in FIG. 2 (100 pmol MAD7-4NLS) and Lonza recommended nucleofection programs SE-CK-116 and SE-CL-120, as well as the two best nucleofection programs observed in this study, SF-CA-137 and SG-CA-138 (FIGS. 3-5 ). Dark grey bars represent mean modification frequency using crDNMT1. Light grey bars represent mean modification frequency using crIDTneg (Integrated DNA Technologies, IDT).

Example 12: Scalable High-Level MAD7-RNP Editing of Immunologically Relevant Genes in Jurkate T-Cell Leukemia Cell Line

The Jurkat T-cell leukemia cell line was used as a model system to screen GNAs demonstrating high editing efficiency. The screen included 298 unique gNAs comprising one or more spacer sequences of SEQ ID NOs: 86-384 of Table 1 targeting the immune checkpoint receptors PDCD1, TIM3, LAG3, TIGIT, and CTLA4, the checkpoint phosphatases PTPN6 (SHP-1) and PTPN11 (SHP-2), and the TCR signaling subunit CD247 (CD3ζ). RNPs were generated as described in Example 3, nucleofected (Example 5), genomic DNA was extracted (Example 8), the edited loci amplified and sequenced (Example 9), and the sequencing data computationally analyzed (Example 10) using the CRISPResso2 algorithm.

CRISPResso2 software reports the frequency of modifications (insertions, deletions, and substitutions) within a quantification window flanking the position of MAD7-induced cleavage in the amplicon sequence. To better understand detection of editing events, the type of modifications detected in 230 amplicons that were sequenced in both gNA-treated and MOCK samples (no MAD7) were compared. Relatively high modification frequencies (median 1%) in MOCK reactions were observed as a result of high frequency of substitutions (FIG. 7 , light grey bars); substitutions were detected at a median frequency of 0.96%, likely due to the errors in NGS base calling or substitutions arising during DNA amplification, while insertions and deletions were found at a much lower median frequency of 0.003% and 0.042%, respectively. Specifically, FIG. 7 shows editing frequency at eight different loci using 298 gNAs (n=3; Mean±SD) in T-cell leukemic cell line as a function of various editing types: all modifications, only insertions, only deletions, only substitutions, or insertions and deletions (INDELs). Edits were achieved using the transfection conditions identified in Example 11, FIG. 2 (100 pmol MAD7-4NLS) and one of the tested Lonza nucleofection programs (FIG. 6 ; SF-CA-137). Dark grey boxplots represent mean modification frequency using gNAs. Light grey boxplots represent mean modification frequency using crIDTneg (IDT). Thus, the frequency of both insertions and deletions (INDEL) were used as a means to quantify the editing activity of the CRISPR-MAD7 system to minimize low end noise. Moreover, low INDEL frequencies in MOCK reactions enabled sensitive detection of editing events at a significantly greater fraction of sites (Fisher exact test, P=3×10⁻¹²; FIG. 8 ). Analysis of gNAs with low INDEL frequencies showed statistically significant editing in gNA-treated samples compared to MOCK samples at INDEL frequencies as low as 0.5% (Fisher exact test, P=4×10⁻⁸; FIG. 8 ). This indicates the sensitivity of the assay to detect modifications in the sub-1% range. Specifically, FIG. 8 shows INDEL frequency at eight different loci using 298 gNAs (n=3; Mean±SD) in T-cell leukemic cell line as a function of two modification types: all modifications <1%, and INDELs <1%, or <0.5%, or <0.1%, with lower INDEL frequencies in MOCK compared to gNA reactions at INDELs <1% (Fisher's exact test; P=3×10⁻¹²) and <0.5% (Fisher exact test, P=4×10⁻⁸). Dark grey boxplots represent mean INDEL frequency using gNAs. Light grey boxplots represent mean INDEL frequency using crIDTneg (IDT).

Since MAD7 can target a wide range of PAM, gNAs adjacent to all YTTN PAM variants were screened and editing specificity of MAD7 in Jurkat cells was analyzed. MAD7 demonstrated editing with all eight combinations of YTTN PAM; in this experiment, editing was higher at the YTTV and TTTV consensus sequences (Fisher exact test; P=2×10⁻³ and P=2×10⁻⁴, respectively). While the majority of highly-active (>50% INDEL frequency) gNAs were found at sites with YTTV and TTTV PAMs, moderately-active (>10% INDEL frequency) gNAs were found to target every PAM sequence with the exception of CTTT. This indicates that MAD7 can edit a wide range of target PAMs, albeit at reduced frequencies (FIG. 9 ). Specifically, FIG. 9 shows INDEL frequency at eight different loci using 298 gNAs (n=3; Mean±SD) in T-cell leukemic cell line as a function of eight YTTN PAM combinations, and TTTV, YTTN, and YTTV PAM motifs. A grey zone on the plot represents moderately-active gNAs (10-50% INDELs), the zone above highly-active gNAs (>50% INDELs), and the zone below active gNAs (1-10% INDELs). INDEL frequency at the YTTV and TTTV PAM motif is significantly higher compared to YTTN motif (Fisher exact test, P=2×10⁻³ and P=2×10⁻⁴, respectively).

Given the large number of gNAs analyzed, it was determined if the targeted DNA sequence biases editing efficiency. Sequence logos were made to compare the DNA-complementary gNA sequences of inactive (<1% INDELs), active (1-10% INDELs), moderately-active (10-50% INDELs), and highly-active (>50% INDELs) gNAs (FIG. 10A). While no strong biases for ribonucleotides at specific positions were identified in this experiment, guanine appeared overrepresented and uracil underrepresented on moderately-active and highly-active gNAs. Next, the frequency of ribonucleotide bases were analyzed within the same four classes of gNAs (FIG. 10B). The analysis confirmed significant enrichment of guanine and depletion of uracil on highly-active gNAs. Specifically, FIG. 10 shows (A) sequence logos comparing DNA-complementary gNA sequences of highly-active (>50% INDELs), moderately-active (10-50% INDELs), active (1-10% INDELs), and inactive (<1% INDELs) gNAs show no strong biases for ribonucleotides at specific positions, however, guanine appeared overrepresented and uracil underrepresented on highly-active and moderately-active gNAs; (B) nucleotide frequency on inactive (<1% INDELs; dark grey box), active (1-10% INDELs; medium grey box), moderately-active (10-50% INDELs; light grey box), and highly-active (>50% INDELs; white box) gNAs, with significant enrichment of guanine and depletion of uracil on highly-active gNAs compared to inactive gNAs (Fisher exact test, P=4×10⁻³ and P=3×10⁻⁴, respectively). Also, significant enrichment of guanine-cytosine content and depletion of adenine-uracil content was observed on moderately-active gNAs compared to inactive gNAs (Fisher exact test, P=1×10⁻²). Moreover, the data showed that nearly 40% of inactive gNAs had runs of three or more adenine or uracil ribonucleotides, while none of the highly-active and <20% of moderately-active gNAs contained such runs (FIG. 11 ). These sequence features can act as an algorithm for selecting putative high-activity gNAs during initial rounds of screening, and could reduce the overall cost of identifying gNAs for various genes of interest. Specifically, FIG. 11 shows fraction of gNAs with AAA and/or UUU runs as a function of INDEL frequency of highly-active (>50% INDELs), moderately-active (10-50% INDELs), active (1-10% INDELs), and inactive (<1% INDELs) gNAs. Fraction of inactive (<1% INDELs) and active (1-10% INDELs) gNAs containing such runs is higher compared to highly-active (>50% INDELs) gNAs (Fisher exact test, P=1×10⁻³ and P=4×10⁻⁴, respectively).

Example 13: Validation of gNAs for Gene Editing and Disruption of Immunologically Relevant Genes Using T-Cell Leukemia Line

High-efficiency gNAs identified in our initial analysis were validated by assaying INDEL frequency for the top three or five gNAs for each of the selected immunologically relevant genes (FIG. 12 ). Specifically, FIG. 12 shows INDEL (dark grey bars) and frameshift (light grey bars) frequencies (n=3; Mean±SD) in T-cell leukemic cell line as a function of 38 high-efficiency gNAs. Alternating grey and white zones on the plot represent groups of three to five high-efficiency gNAs per locus. In the validation experiment, the INDEL frequency was significantly correlated to the measurements from the initial screen, highlighting the reproducibility of the INDEL assay (FIG. 13 ). Specifically, FIG. 13 shows correlation of INDEL frequency in the gNA validation experiment versus INDEL formation in the gNA screen experiment (Spearman's correlation=0.91; P=9×10⁻¹⁴), highlighting reproducibility of the INDEL assay. Using the CRISPresso2 software, the degree of open reading frame (ORF) disruption for each of the validated gNAs was estimated (FIG. 12 ). In addition, for four high-efficiency gNAs targeting three different exons at the PDCD1 locus, surface expression of the PDCD1 protein was measured by flow cytometry 4, 7, and 11 days post-transfection (data not shown). The data revealed that the protein surface expression after transfection with crPDCD1_2, a gNA targeting the PDCD1 gene at the extracellular domain of the protein, was as low as 10% 4 days post-transfection and remained at this level even at day 11 post-transfection. The surface expression after transfection with the remaining three gNAs was significantly higher, 35% and 85% after transfection with crPDCD1_3 and both crPDCD1_4 and crPDCD1_5, respectively. This is in line with the ORF data analysis, which showed that for most of the gNAs including the high-efficiency crPDCD1s, the predicted number of INDELs leading to frameshifts was similar to that expected from an unbiased DNA repair process, with frameshifts in two-thirds of the edited loci (FIG. 14 ). However, several of the gNAs had a markedly different degree of ORF disruption; crCD247_4 resulted in frameshifts with 97% frequency, while crTIM3_1 and crTIM3_3 resulted in frameshifts with 23% and 44% frequency, respectively (FIG. 14 ). Specifically, FIG. 14 shows fraction of frameshift to INDEL frequency (dark grey bars) in T-cell leukemic cell line as a function of 38 high-efficiency gNAs. Average fraction of INDELs leading to frameshifts (dashed line) is approx. 66%. Alternating grey and white zones on the plot represent groups of three to five high-efficiency gNAs per locus. The analysis of repair products indicates that in the case of crTIM3_1, and to some extent crTIM3_3, the bias arose from directly repeated sequences at the DNA cleavage site, which possibly promoted microhomology-mediated end joining (MMEJ) repair following DNA cleavage. These data help inform selection of gNAs for gene KO since some gNAs, such as crTIM3_1, have much lower frequency of gene disruption than would be predicted based on the frequency of INDEL formation.

Another consideration for selecting gNAs is the potential for off-target cleavage events. The list of validated gNAs was analyzed using the CasOFFinder software to predict potential off-target editing sites in the genome with up to four mismatches between the gNA and the target DNA sequence. Using the Bioconductor R packages, the predicted off-target sites were matched with the human gene database, and those sites that targeted exons and introns within the genes were extracted. Afterwards, the degree of editing activity at these sites was examined by targeted next-generation sequencing, more specifically, at 25 predicted off-target sites for the top-two PDCD1 gNAs, i.e., crPDCD1_1 and crPDCD1_2. The analysis revealed low-level off-target activity at crPDCD1_2_13 and crPDCD1_2_15 sites, however, INDEL formation at these two sites was statistically insignificant compared to MOCK samples (non-targeting gNAs) (Pairwise T-test, P≥0.05; FIGS. 15 and 16 ). INDEL frequency at 43 putative off-target sites with up to three mismatches between gNA and target DNA sequence were assayed for the top-two gNAs targeting seven remaining genes (i.e., TIM3, LAG3, TIGIT, CTLA4, PTPN6, PTPN11, and CD247; spacer sequences in Table 1). The analysis revealed no detectable activity at any of the putative off-target sites (FIGS. 15 and 16 ), which confirms the high cleavage fidelity of MAD7-gNA complexes. Specifically, FIGS. 15-16 show INDEL frequency of MAD7 (n=3; Mean±SD) in T-cell leukemic cell line at predicted off-target sites analyzed by targeted deep sequencing. For crPDCD1, INDEL frequency was analyzed at the putative off-target editing sites with ≤4 mismatches between the gNA and target DNA sequence, and with ≤3 mismatches on the remaining gNAs. PAM sequences and spacer sequences with mismatches marked in red are displayed next to their respective measured INDEL frequencies. No significant INDEL frequency at any of the off-target sites was detected (Pairwise T-test, P≥0.05).

Insertion of exogenous transgenes is an important aspect of mammalian cell engineering. Gene insertion with CRISPR-Cas is achieved by homology-directed repair of CRISPR-induced DNA breaks using HDR-donor templates to copy exogenous genetic sequences into targeted DNA loci. Several studies indicate that HDR templates, composed of linear double stranded DNA, provide the most robust and efficient method of transgene insertion using CRISPR-Cas genome editing systems.

The Jurkat T-cell leukemia cell line was used to evaluate the transgene insertion and expression efficiency using CRISPR-MAD7 RNP complexes. A highly active gNA targeting the AAVS1 (spacer sequence in Table 1) safe-harbor locus (FIG. 17 ) was used in combination with eight different HDR-repair templates flanked with symmetric homology arms (HA) of 500 base pairs (bp) in the amount of 0.5 μg μL⁻¹. Specifically, FIG. 17 shows INDEL frequency at the AAVS1 locus (n=3; Mean±SD) in T-cell leukemic cell line as a function of MAD7-RNP amounts (pmol; constant ratio of 1:1.5 MAD7:gNA). Dark grey bars represent mean INDEL frequency using crAAVS1. Light grey bars represent mean modification frequency using crIDTneg (IDT). The HDR inserts comprised eight promoters (Table 2) differing in both size and promoter strength to drive GFP expression (FIG. 18 ). When the transient GFP expression diminished at day 14 post-transfection, comparable insertion efficiencies were observed with stable GFP expressions of up to 30% using four (JET, PGK, EF1a, and CAG) out of eight promoters (FIG. 18 ), suggesting that the insert size has not affected the integration efficiency at AAVS1 in human T-cell leukemia cell line. Specifically, FIG. 18 shows GFP insertion efficiency at AAVS1 (n=3; Mean±SD) and cell viability of T-cell leukemic cell line measured at day 14 post-transfection. HDR templates consisting of eight different promoters and flanked with symmetric homology arms of 500 base pairs in the amount of 0.5 μg μL⁻¹ were used. Size of promoters in base pairs: CMV, 1400; SCP, 970; CMVe-SCP, 1270; CMVmax, 1830; JET, 1100; CAG, 2600; PGK, 1410; EF-1α, 2090. Dark grey bars and circles present mean insertion frequency and cell viability using crAAVS1. Light grey bars represent mean insertion frequency and cell viability using crIDTneg (IDT).

TABLE 2 SEQ Name ID NO Sequence CMV 413 CGTTACATAACTTACGGTAA ATGGCCCGCCTGGCTGACCG CCCAACGACCCCCGCCCATT GACGTCAATAATGACGTATG TTCCCATAGTAACGCCAATA GGGACTTTCCATTGACGTCA ATGGGTGGAGTATTTACGGT AAACTGCCCACTTGGCAGTA CATCAAGTGTATCATATGCC AAGTACGCCCCCTATTGACG TCAATGACGGTAAATGGCCC GCCTGGCATTATGCCCAGTA CATGACCTTATGGGACTTTC CTACTTGGCAGTACATCTAC GTATTAGTCATCGCTATTAC CATGGTGATGCGGTTTTGGC AGTACATCAATGGGCGTGGA TAGCGGTTTGACTCACGGGG ATTTCCAAGTCTCCACCCCA TTGACGTCAATGGGAGTTTG TTTTGGCACCAAAATCAACG GGACTTTCCAAAATGTCGTA ACAACTCCGCCCCATTGACG CAAATGGGCGGTAGGCGTGT ACGGTGGGAGGTCTATATAA GCAGAGCT SCP 414 GTACTTATATAAGGGGGTGG GGGCGCGTTCGTCCTCAGTC GCGATCGAACACTCGAGCCG AGCAGACGTGCCTACGGACC G CMVe- 415 CGTTACATAACTTACGGTAA SCP ATGGCCCGCCTGGCTGACCG CCCAACGACCCCCGCCCATT GACGTCAATAATGACGTATG TTCCCATAGTAACGCCAATA GGGACTTTCCATTGACGTCA ATGGGTGGAGTATTTACGGT AAACTGCCCACTTGGCAGTA CATCAAGTGTATCATATGCC AAGTACGCCCCCTATTGACG TCAATGACGGTAAATGGCCC GCCTGGCATTATGCCCAGTA CATGACCTTATGGGACTTTC CTACTTGGCAGTACATCTAC GTATTAGTCATCGCTATTAC CATGGTACTTATATAAGGGG GTGGGGGCGCGTTCGTCCTC AGTCGCGATCGAACACTCGA GCCGAGCAGACGTGCCTACG GACCG CMVmax 416 TCAATATTGGCCATTAGCCA TATTATTCATTGGTTATATA GCATAAATCAATATTGGCTA TTGGCCATTGCATACGTTGT ATCTATATCATAATATGTAC ATTTATATTGGCTCATGTCC AATATGACCGCCATGTTGGC ATTGATTATTGACTAGTTAT TAATAGTAATCAATTACGGG GTCATTAGTTCATAGCCCAT ATATGGAGTTCCGCGTTACA TAACTTACGGTAAATGGCCC GCCTGGCTGACCGCCCAACG ACCCCCGCCCATTGACGTCA ATAATGACGTATGTTCCCAT AGTAACGCCAATAGGGACTT TCCATTGACGTCAATGGGTG GAGTATTTACGGTAAACTGC CCACTTGGCAGTACATCAAG TGTATCATATGCCAAGTCCG CCCCCTATTGACGTCAATGA CGGTAAATGGCCCGCCTGGC ATTATGCCCAGTACATGACC TTACGGGACTTTCCTACTTG GCAGTACATCTACGTATTAG TCATCGCTATTACCATGGTG ATGCGGTTTTGGCAGTACAC CAATGGGCGTGGATAGCGGT TTGACTCACGGGGATTTCCA AGTCTCCACCCCATTGACGT CAATGGGAGTTTGTTTTGGC ACCAAAATCAACGGGACTTT CCAAAATGTCGTAATAACCC CGCCCCGTTGACGCAAATGG GCGGTAGGCGTGTACGGTGG GAGGTCTATATAAGCAGAGG TCGTTTAGTGAACCGTCAGA TCACTAGTAGCTTTATTGCG GTAGTTTATCACAGTTAAAT TGCTAACGCAGTCAGTGCTC GACTGATCACAGGTAAGTAT CAAGGTTACAAGACAGGTTT AAGGAGGCCAATAGAAACTG GGCTTGTCGAGACAGAGAAG ATTCTTGCGTTTCTGATAGG CACCTATTGGTCTTACTGAC ATCCACTTTGCCTTTCTCTC CACAGGG JET 417 GAATTCGGGCGGAGTTAGGG CGGAGCCAATCAGCGTGCGC CGTTCCGAAAGTTGCCTTTT ATGGCTGGGCGGAGAATGGG CGGTGAACGCCGATGATTAT ATAAGGACGCGCCGGGTGTG GCACAGCTAGTTCCGTCGCA GCCGGGATTTGGGTCGCGGT TCTTGTTTGTGGATCCCTGT GATCGTCACTTGACA CAG 418 ATCTCGACTAGTTATTAATA GTAATCAATTACGGGGTCAT TAGTTCATAGCCCATATATG GAGTTCCGCGTTACATAACT TACGGTAAATGGCCCGCCTG GCTGACCGCCCAACGACCCC CGCCCATTGACGTCAATAAT GACGTATGTTCCCATAGTAA CGCCAATAGGGACTTTCCAT TGACGTCAATGGGTGGAGTA TTTACGGTAAACTGCCCACT TGGCAGTACATCAAGTGTAT CATATGCCAAGTACGCCCCC TATTGACGTCAATGACGGTA AATGGCCCGCCTGGCATTAT GCCCAGTACATGACCTTATG GGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCATC GCTATTACCATGGTCGAGGT GAGCCCCACGTTCTGCTTCA CTCTCCCCATCTCCCCCCCC TCCCCACCCCCAATTTTGTA TTTATTTATTTTTTAATTAT TTTGTGCAGCGATGGGGGCG GGGGGGGGGGGGGGGCGCGC GCCAGGCGGGGCGGGGCGGG GCGAGGGGCGGGGCGGGGCG AGGCGGAGAGGTGCGGCGGC AGCCAATCAGAGCGGCGCGC TCCGAAAGTTTCCTTTTATG GCGAGGCGGCGGCGGCGGCG GCCCTATAAAAAGCGAAGCG CGCGGCGGGCGGGGAGTCGC TGCGACGCTGCCTTCGCCCC GTGCCCCGCTCCGCCGCCGC CTCGCGCCGCCCGCCCCGGC TCTGACTGACCGCGTTACTC CCACAGGTGAGCGGGCGGGA CGGCCCTTCTCCTCCGGGCT GTAATTAGCGCTTGGTTTAA TGACGGCTTGTTTCTTTTCT GTGGCTGCGTGAAAGCCTTG AGGGGCTCCGGGAGGGCCCT TTGTGCGGGGGGAGCGGCTC GGGGGGTGCGTGCGTGTGTG TGTGCGTGGGGAGCGCCGCG TGCGGCTCCGCGCTGCCCGG CGGCTGTGAGCGCTGCGGGC GCGGCGCGGGGCTTTGTGCG CTCCGCAGTGTGCGCGAGGG GAGCGCGGCCGGGGGCGGTG CCCCGCGGTGCGGGGGGGGC TGCGAGGGGAACAAAGGCTG CGTGCGGGGTGTGTGCGTGG GGGGGTGAGCAGGGGGTGTG GGCGCGTCGGTCGGGCTGCA ACCCCCCCTGCACCCCCCTC CCCGAGTTGCTGAGCACGGC CCGGCTTCGGGTGCGGGGCT CCGTACGGGGCGTGGCGCGG GGCTCGCCGTGCCGGGCGGG GGGTGGCGGCAGGTGGGGGT GCCGGGCGGGGCGGGGCCGC CTCGGGCCGGGGAGGGCTCG GGGGAGGGGCGCGGCGGCCC CCGGAGCGCCGGCGGCTGTC GAGGCGCGGCGAGCCGCAGC CATTGCCTTTTATGGTAATC GTGCGAGAGGGCGCAGGGAC TTCCTTTGTCCCAAATCTGT GCGGAGCCGAAATCTGGGAG GCGCCGCCGCACCCCCTCTA GCGGGCGCGGGGCGAAGCGG TGCGGCGCCGGCAGGAAGGA AATGGGCGGGGAGGGCCTTC GTGCGTCGCCGCGCCGCCGT CCCCTTCTCCCTCTCCAGCC TCGGGGCTGTCCGCGGGGGG ACGGCTGCCTTCGGGGGGGA CGGGGCAGGGCGGGGTTCGG CTTCTGGCGTGTGACCGGCG GCTCTAGAGCCTCTGCTAAC CATGTTCATGCCTTCTTCTT TTTCCTACAGCTCCTGGGCA ACGTGCTGGTTATTGTGCTG TCTCATCATTTTGGCAAAGA ATT PGK 419 GGGGTTGGGGTTGCGCCTTT TCCAAGGCAGCCCTGGGTTT GCGCAGGGACGCGGCTGCTC TGGGCGTGGTTCCGGGAAAC GCAGCGGCGCCGACCCTGGG TCTCGCACATTCTTCACGTC CGTTCGCAGCGTCACCCGGA TCTTCGCCGCTACCCTTGTG GGCCCCCCGGCGACGCTTCC TGCTCCGCCCCTAAGTCGGG AAGGTTCCTTGCGGTTCGCG GCGTGCCGGACGTGACAAAC GGAAGCCGCACGTCTCACTA GTACCCTCGCAGACGGACAG CGCCAGGGAGCAATGGCAGC GCGCCGACCGCGATGGGCTG TGGCCAATAGCGGCTGCTCA GCAGGGCGCGCCGAGAGCAG CGGCCGGGAAGGGGCGGTGC GGGAGGCGGGGTGTGGGGCG GTAGTGTGGGCCCTGTTCCT GCCCGCGCGGTGTTCCGCAT TCTGCAAGCCTCCGGAGCGC ACGTCGGCAGTCGGCTCCCT CGTTGACCGAATCACCGACC TCTCTCCCCAG EF-1a 420 GAATTCAGGCTCCGGTGCCC GTCAGTGGGCAGAGCGCACA TCGCCCACAGTCCCCGAGAA GTTGGGGGGAGGGGTCGGCA ATTGAACCGGTGCCTAGAGA AGGTGGCGCGGGGTAAACTG GGAAAGTGATGTCGTGTACT GGCTCCGCCTTTTTCCCGAG GGTGGGGGAGAACCGTATAT AAGTGCAGTAGTCGCCGTGA ACGTTCTTTTTCGCAACGGG TTTGCCGCCAGAACACAGGT AAGTGCCGTGTGTGGTTCCC GCGGGCCTGGCCTCTTTACG GGTTATGGCCCTTGCGTGCC TTGAATTACTTCCACCTGGC TGCAGTACGTGATTCTTGAT CCCGAGCTTCGGGTTGGAAG TGGGTGGGAGAGTTCGAGGC CTTGCGCTTAAGGAGCCCCT TCGCCTCGTGCTTGAGTTGA GGCCTGGCCTGGGCGCTGGG GCCGCCGCGTGCGAATCTGG TGGCACCTTCGCGCCTGTCT CGCTGCTTTCGATAAGTCTC TAGCCATTTAAAATTTTTGA TGACCTGCTGCGACGCTTTT TTTCTGGCAAGATAGTCTTG TAAATGCGGGCCAAGATCTG CACACTGGTATTTCGGTTTT TGGGGCCGCGGGCGGCGACG GGGCCCGTGCGTCCCAGCGC ACATGTTCGGCGAGGCGGGG CCTGCGAGCGCGGCCACCGA GAATCGGACGGGGGTAGTCT CAAGCTGGCCGGCCTGCTCT GGTGCCTGGTCTCGCGCCGC CGTGTATCGCCCCGCCCTGG GCGGCAAGGCTGGCCCGGTC GGCACCAGTTGCGTGAGCGG AAAGATGGCCGCTTCCCGGC CCTGCTGCAGGGAGCTCAAA ATGGAGGACGCGGCGCTCGG GAGAGCGGGCGGGTGAGTCA CCCACACAAAGGAAAAGGGC CTTTCCGTCCTCAGCCGTCG CTTCATGTGACTCCACGGAG TACCGGGCGCCGTCCAGGCA CCTCGATTAGTTCTCGAGCT TTTGGAGTACGTCGTCTTTA GGTTGGGGGGAGGGGTTTTA TGCGATGGAGTTTCCCCACA CTGAGTGGGTGGAGACTGAA GTTAGGCCAGCTTGGCACTT GATGTAATTCTCCTTGGAAT TTGCCCTTTTTGAGTTTGGA TCTTGGTTCATTCTCAAGCC TCAGACAGTGGTTCAAAGTT TTTTTCTTCCATTTCAGGTG TCGTGACATCATTTT

Subsequently, keeping the MAD7-RNP amounts constant, the effect of various homology arm lengths (100 vs 500 bp) and HDR template amounts (0.125 μg μL⁻¹, 0.25 μg μL⁻¹, 0.5 μg μL⁻¹, and 1 μg μL⁻¹) on the insertion efficiency was evaluated using JET and EF1a promoters. Up to 30% higher integration efficiency was observed with HDR templates flanked with HA of 500 compared to 100 base pairs. Moreover, the data showed improved insertion efficiencies with increasing amounts of HDR templates flanked with either 100 or 500 base pair HA but at the same time somewhat reduced cell viability (FIG. 19 ). Specifically, FIG. 19 shows GFP insertion efficiency at AAVS1 (n=3; Mean±SD) in T-cell leukemic cell line measured at days 2, 7, 14, and 21 post-transfection as a function of donor template amount. No transient GFP expression was observed at day 21 post-transfection. Cell viability (black circles) was measured at day 2 post-transfection. Top panels display GFP insertion efficiencies using donor template flanked with short homology arms (100 bp HA), and bottom panels donor template flanked with long homology arms (500 bp HA). Left panels display GFP insertion efficiencies using donor template containing EF-1α promoter (long, ˜2000 bp), and right panels donor template containing JET promoter (short, ˜1000 bp). Amount of donor template, represented by the gradient above the bars, increases from 0.125, 0.25, 0.5 to 1 μg μL⁻¹. Dark grey bars represent mean insertion frequency using crAAVS1. Light grey bars represent mean insertion frequency using crIDTneg (IDT).

Next, using primary T-cells isolated from the human peripheral blood from three donors and a protocol selected from the experiments above, i.e., 150:100 pmol gNA:MAD7 RNP complex together with 1 μg μL⁻¹ HDR template, in combination with 100 μg μL⁻¹ poly-L-glutamic acid (PGA), integration efficiency of a clinically relevant CAR transgene containing JET or EF1a promoter flanked with HA of 100 or 500 base pairs and a bovine growth hormone derived polyadenylation sequence was analyzed. An anti-CD19 CAR with fully human variable regions (Hu19CAR), CD8α hinge and transmembrane domains, a CD28 costimulatory domain, and CD3ζ activation domain was used. Moderate insertion efficiency at AAVS1 but stable CAR expression of up to 14% and 16% was observed using HDR templates flanked with 100 and 500 base pair HA, respectively. The normalized cell viability measured 24 h post-transfection was in same cases relatively low, ranging from 22% with JET-500-CAR, 35% with JET-100-CAR, 43% with EF1a-100-CAR, to 55% with EF1a-500-CAR (FIG. 20 ). It is important to emphasize, that both CAR insertion efficiency and cell viability were higher in the treatment with PGA compared to the treatment without PGA (P≤0.05; data not shown). Specifically, FIG. 20 shows CAR insertion efficiency at AAVS1 (D=3; n=3; Mean±SD) in primary Pan T-cells measured at days 7 and 11 post-transfection. Cell viability was measured 24 hours post-transfection. Individual panels display CAR insertion efficiencies using donor template structure as described in FIG. 19 . Amount of donor template, MAD7-RNP, and PGA was 1 μg μL⁻¹, 100:150 pmol MAD7:gNA, and 100 μg μL⁻¹, in that order. Nucleofection program P3-EH-115 for transfection of primary T-cells was used. D represents number of biological replicas, and n number of technical replicas per D. Dark grey bars represent mean insertion frequency using crAAVS1. Light grey bars represent mean insertion frequency using crIDTneg (IDT).

Multiple parameters were reevaluated to further optimize primary T-cell viability and CAR insertion efficiencies at AAVS1. Using Pan T-cells isolated from the blood from two donors, the effect of RNP amount with 100 μg μL⁻¹ PGA and EF1a-500-CAR template amount on CAR insertion efficiency and cell viability was tested (data not shown). Reducing the RNP amount to 75:50 pmol gNA:MAD7 RNP complex while increasing the donor template amount to 1.5 μg μL⁻¹ led to improved CAR insertion efficiencies without significantly affecting cell viability (P≥0.05; data not shown). In addition, using the abovementioned transfection conditions in combination with the cell recovery in a post-transfection cultivation medium pretreated with 2 μM M3814 resulted in nearly 5-times more efficient CAR insertion than other experiments (FIG. 21 ). The optimized CRISPR-MAD7 transfection protocol resulted in CAR insertion efficiency of up to 85% 13-days post-transfection (median 65%) together with the median normalized cell viability as high as 62% 24 hours post-transfection. Specifically, FIG. 21 shows CAR insertion efficiency at AAVS1 (D=5; n=3) in primary Pan T-cells measured at day 7 post-transfection, and re-measured in two biological replicas at day 13 post-transfection (D=2; n=3). Cell viability was measured 24 hours post-transfection (D=5; n=3; Mean±SD). Amount or concentration of donor template, MAD7-RNP, PGA, and M3814 was 1.5 μg μL⁻¹, 50:75 pmol MAD7:gNA, 100 μg μL⁻¹, and 2 μM, respectively. Nucleofection program P3-EH-115 for transfection of primary T-cells was used. D represents number of biological replicas, and n number of technical replicas per D. Dark grey bars represent mean insertion frequency using crAAVS1. Light grey bars represent mean insertion frequency using crIDTneg (IDT).

EQUIVALENTS

Throughout the description, where compositions are described as having, including, or comprising specific components, or where processes and methods are described as having, including, or comprising specific steps, it is contemplated that, additionally, there are compositions of the present invention that consist essentially of, or consist of, the recited components, and that there are processes and methods according to the present invention that consist essentially of, or consist of, the recited processing steps.

In the application, where an element or component is said to be included in and/or selected from a list of recited elements or components, it should be understood that the element or component can be any one of the recited elements or components, or the element or component can be selected from a group consisting of two or more of the recited elements or components.

Further, it should be understood that elements and/or features of a composition or a method described herein can be combined in a variety of ways without departing from the spirit and scope of the present invention, whether explicit or implicit herein. For example, where reference is made to a particular compound, that compound can be used in various embodiments of compositions of the present invention and/or in methods of the present invention, unless otherwise understood from the context. In other words, within this application, embodiments have been described and depicted in a way that enables a clear and concise application to be written and drawn, but it is intended and will be appreciated that embodiments may be variously combined or separated without parting from the present teachings and invention(s). For example, it will be appreciated that all features described and depicted herein can be applicable to all aspects of the invention(s) described and depicted herein.

The terms “a” and “an” and “the” and similar references in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. For example, the term “a cell” includes a plurality of cells, including mixtures thereof. Where the plural form is used for compounds, salts, or the like, this is taken to mean also a single compound, salt, or the like.

It should be understood that the expression “at least one of” includes individually each of the recited objects after the expression and the various combinations of two or more of the recited objects unless otherwise understood from the context and use. The expression “and/or” in connection with three or more recited objects should be understood to have the same meaning unless otherwise understood from the context.

The use of the term “include,” “includes,” “including,” “have,” “has,” “having,” “contain,” “contains,” or “containing,” including grammatical equivalents thereof, should be understood generally as open-ended and non-limiting, for example, not excluding additional unrecited elements or steps, unless otherwise specifically stated or understood from the context.

Where the use of the term “about” is before a quantitative value, the present invention also includes the specific quantitative value itself, unless specifically stated otherwise. As used herein, the term “about” refers to a ±10% variation from the nominal value unless otherwise indicated or inferred.

It should be understood that the order of steps or order for performing certain actions is immaterial so long as the present invention remain operable. Moreover, two or more steps or actions may be conducted simultaneously.

The use of any and all examples, or exemplary language herein, for example, “such as” or “including,” is intended merely to illustrate better the present invention and does not pose a limitation on the scope of the invention unless claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the present invention.

The invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting on the invention described herein. Scope of the invention is thus indicated by the appended claims rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein.

Embodiments

In embodiment 1 provided herein is a composition comprising a nucleic acid-guided nuclease comprising a Type V CRISPR nuclease polypeptide comprising at least one nuclear localization signal (NLS) at or near the N-terminus or the C-terminus of the polypeptide. In embodiment 2 provided herein is the composition of embodiment 1 wherein the nuclease is a Type Va nuclease. In embodiment 3 provided herein is the composition of embodiment 1 or embodiment 2 wherein the Type V CRISPR nuclease polypeptide has at least 60, 70, 80, 85, 90, 95, 96, 97, 98, 99, or 100% sequence identity, preferably at least 80%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% sequence identity with SEQ ID NO: 1. In embodiment 4 provided herein is the composition of any previous embodiment wherein the Type V CRISPR nuclease polypeptide comprises two NLSs, one or both of which are at or near the N-terminus or the C-terminus of the polypeptide. In embodiment 5 provided herein is the composition of any previous embodiment wherein the Type V CRISPR nuclease polypeptide comprises three NLSs, each of which is at or near the N-terminus or the C-terminus of the polypeptide. In embodiment 6 provided herein is the composition of any previous embodiment wherein the Type V CRISPR nuclease polypeptide comprises four NLSs, each of which is at or near the N-terminus or the C-terminus of the polypeptide. In embodiment 7 provided herein is the composition of any previous embodiment wherein the Type V CRISPR nuclease polypeptide comprises at least five NLSs, each of which is at or near the N-terminus or the C-terminus of the polypeptide. In embodiment 8 provided herein is the composition of any one of embodiments 4 through 7 wherein at least two of the NLSs are at or near the N-terminus of the polypeptide. In embodiment 9 provided herein is the composition of any one of embodiments 5 through 7 wherein at least three of the NLSs are at or near the N-terminus of the polypeptide. In embodiment 10 provided herein is the composition of any one of embodiments 6 through 7 wherein at least four of the NLSs are at or near the N-terminus of the polypeptide. In embodiment 11 provided herein is the composition of embodiment 7 wherein the 5 NLSs are at or near the N-terminus of the polypeptide. In embodiment 12 provided herein is the composition of embodiment 11 comprising a sequence at least 60, 70, 80, 85, 90, 95, 98, 99%, or 100%, identical, preferably at least 80%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% identical to any one of SEQ ID NOs: 109-112. In embodiment 13 provided herein is the composition of any one of embodiments 1 through 3 wherein the Type V CRISPR nuclease polypeptide comprises at least 1-30, 1-20, 1-15, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 2-30, 2-20, 2-15, 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 3-30, 3-20, 3-15, 3-10, 3-9, 3-8, 3-7, 3-6, or 3-5, preferably 1-10, more preferably 2-10, even more preferably 3-10 NLSs, each of which is at or near the N-terminus or the C-terminus of the polypeptide. In embodiment 14 provided herein is the composition of any one of embodiments 4 through 11 wherein at least two of the NLSs have different nuclear localization mechanisms. In embodiment 15 provided herein is the composition of any one of embodiments 5 through 7 or 9 through 11 wherein at least three of the NLSs have different nuclear localization mechanisms. In embodiment 16 provided herein is the composition of any previous embodiment wherein one or more of the NLSs comprises an NLS of the SV40 virus large T-antigen, an NLS from nucleoplasmin, e.g. a nucleoplasmin bipartite NLS, a c-myc NLS; a hRNPA1 M9 NLS; an IBB domain of importin-alpha NLS; a myoma T protein NLS; a sequence from human p53 NLS; a sequence of mouse c-abl IV NLS; a sequence of influenza virus NS1 NLS; a sequence of Hepatitis virus delta antigen NLS; a sequence of mouse Mx1 protein NLS; a sequence of human poly(ADP-ribose) polymerase NLS; a sequence of steroid hormone receptors (human) glucocorticoid NLS; and/or a sequence of EGL-13 NLS. In embodiment 17 provided herein is the composition of embodiment 16 wherein one or more of the NLSs comprises an NLS of the SV40 virus large T-antigen. In embodiment 18 provided herein is the composition of embodiment 16 wherein two or more of the NLSs comprises an NLS of the SV40 virus large T-antigen. In embodiment 19 provided herein is the composition of embodiment 17 or embodiment 18 wherein the NLS or NLSs comprises the sequence of SEQ ID NO: 5. In embodiment 20 provided herein is the composition of any one of embodiments 16 through 19 wherein one or more of the NLSs comprises an NLS from nucleoplasmin. In embodiment 21 provided herein is the composition of embodiment 20 wherein the nucleoplasmin NLS comprises the sequence of SEQ ID NO: 6. In embodiment 22 provided herein is the composition of any one of embodiments 16 through 21 wherein one or more of the NLSs comprises a c-myc NLS. In embodiment 23 provided herein is the composition of embodiment 22 wherein the c-myc NLS comprises the sequence of SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 21. In embodiment 24 provided herein is the composition of embodiment 23 wherein the c-myc NLS comprises the sequence of SEQ ID NO: 21. In embodiment 25 provided herein is the composition of any one of embodiments 16 through 24 wherein one or more of the NLSs comprises a sequence of EGL-13 NLS. In embodiment 26 provided herein is the composition of embodiment 25 wherein the EGL-13 NLS comprises the sequence of SEQ ID NO: 107. In embodiment 27 provided herein is the composition of any previous embodiment wherein the Type V CRISPR nuclease polypeptide further comprises a purification tag. In embodiment 28 provided herein is the composition of embodiment 27 wherein the purification tag is at or near the N-terminus of the nuclease polypeptide. In embodiment 29 provided herein is the composition of embodiment 27 or embodiment 28 wherein the purification tag comprises a poly-his tag, such as a Gly-6×His tag (SEQ ID NO: 421) or Gly-8×His tag (SEQ ID NO: 422); short epitope tags, e.g., FLAG, hemagglutinin (HA), c-myc, T7, Glu-Glu; maltose binding protein (mbp); N-terminal glutathione S-transferase (GST); or calmodulin binding peptide (CBP) In embodiment 30 provided herein is the composition of embodiment 29 wherein the purification tag comprises a poly-his tag. In embodiment 31 provided herein is the composition of embodiment 30 wherein the purification tag comprises a gly-6×His tag (SEQ ID NO: 421). In embodiment 32 provided herein is the composition of embodiment 30 wherein the purification tag comprises a gly-8×His tag (SEQ ID NO: 422). In embodiment 33 provided herein is the composition of any previous embodiment wherein the Type V CRISPR nuclease polypeptide comprises a cleavage site. In embodiment 34 provided herein is the composition of embodiment 33 wherein the cleavage site is at or near the N-terminus of the nuclease polypeptide. In embodiment 35 provided herein is the composition of embodiment 33 or embodiment 34 wherein the cleavage site comprises a Tobacco Etch Virus (TEV) cleavage site. In embodiment 36 provided herein is the composition of embodiment 35 wherein the cleavage site comprises the sequence of SEQ ID NO: 108. In embodiment 37 provided herein is the composition of embodiment 36 comprising 5 NLSs at or near the N-terminus of the polypeptide, a purification tag, and the cleavage site, wherein the cleavage site is after the purification tag. In embodiment 38 provided herein is the composition of embodiment 37 comprising a sequence at least 60, 70, 80, 85, 90, 95, 98, 99%, or 100%, identical, preferably at least 8%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% identical to SEQ ID NO: 111 or 112. In embodiment 39 provided herein is the composition of embodiment 37 comprising a sequence at least 60, 70, 80, 85, 90, 95, 98, 99%, or 100%, identical, preferably at least 8%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% identical to SEQ ID NO: 112. In embodiment 40 provided herein is the composition of any previous embodiment further comprising a guide nucleic acid (gNA), e.g., gRNA, comprising a spacer sequence that targets a target nucleotide sequence within a polynucleotide, or a polynucleotide coding for the gNA, e.g., gRNA, wherein the gNA, e.g., gRNA is compatible with the Type V CRISPR nuclease. In embodiment 41 provided herein is the composition of embodiment 40 wherein the target nucleotide is within 50 nucleotides of a protospacer adjacent motif (PAM) sequence specific for the Type V CRISPR nuclease. In embodiment 42 provided herein is the composition of embodiment 41 wherein the PAM comprises a sequence of YTTN, wherein Y is T or C and N is A, T, G, or C. In embodiment 43 provided herein is the composition of embodiment 42 wherein the PAM comprises a sequence of YTTV or TTTV, wherein V is A, G, or C. In embodiment 44 provided herein is the composition of embodiment 40 wherein the gNA is a gRNA. In embodiment 45 provided herein is the composition of embodiment 44 wherein the gRNA is a dual gRNA. In embodiment 46 provided herein is the composition of embodiment 44 or embodiment 45 wherein the composition comprises the gRNA and the gRNA comprises one or more chemical modifications. In embodiment 47 provided herein is the composition of embodiment 46 wherein the chemical modification comprises a 2′-O-alkyl, a 2′-O-methyl, a phosphorothioate, a phosphonoacetate, a thiophosphonoacetate, a 2′-O-methyl-3′-phosphorothioate, a 2′-O-methyl-3′-phosphonoacetate, a 2′-O-methyl-3′-thiophosphonoacetate, a 2′-deoxy-3′-phosphonoacetate, a 2′-deoxy-3′-thiophosphonoacetate, a suitable alternative, or a combination thereof. In embodiment 48 provided herein is the composition of any one of embodiments 44 through 47 wherein a ratio of guanine:uracil in the gRNA is at least 51:49, 52:48, 53:47, 54:46, 55:45, 56:44, 57:43, 58:42, 59:42, or 60:40, preferably at least 53:47, more preferably at least 54:46, even more preferably at least 55:45. In embodiment 49 provided herein is the composition of any one of embodiments 40 through 48 wherein the molar ratio of gNA, e.g., gRNA to Type V CRISPR nuclease is at least 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 2:1, 2.2:1, 2.5:1, or 3:1 and/or not more than 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 2:1, 2.2:1, 2.5:1, 3:1, or 4:1, preferably 1.1:1 to 2.5:1, more preferably 1.2:1 to 2:1, even more preferably 1.2:1 to 1.7:1. In embodiment 50 provided herein is the composition of any one of embodiments 40 through 49 wherein the molar amount of gNA, e.g., gRNA, is at least 10, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 170, 190 or 200 pmol and/or not more than 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 170, 190, 200, 250, or 300 pmol, preferably 25-200 pmol, more preferably 50-100 pmol, even more preferably 65 to 85 pmol. In embodiment 51 provided herein is the composition of any one of embodiments 40 through 50 further comprising a donor template. In embodiment 52 provided herein is the composition of embodiment 51 wherein the donor template comprises homology arms. In embodiment 53 provided herein is the composition of embodiment 51 or embodiment 52 wherein the donor template is present in an amount of at least 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.7, 2, 2.5, 3, 4, or 5 μg μL−1 and/or not more than 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.7, 2, 2.5, 3, 4, 5, 7, or 10 μg μL−1, preferably 0.3 to 2 μg μL−1, more preferably 0.5 to 1.5 μg μL−1, even more preferably 0.8 to 1.2 μg μL−1. In embodiment 54 provided herein is the composition of any one of embodiments 40 through 53 further comprising an anionic polymer. In embodiment 55 provided herein is the composition of embodiment 54 wherein the anionic polymer comprises polyglutamic acid (PGA). In embodiment 56 provided herein is the composition of embodiment 54 or embodiment 55 wherein the anionic polymer is present at a concentration of at least 20, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 170, 200, 250, 300, 400, or 500 μg μL−1 and/or not more than 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 170, 200, 250, 300, 400, 500, 700, or 1000 μg μL−1, preferably 20 to 200 μg μL−1, more preferably 50 to 150 μg μL−1, even more preferably 80 to 120 μg μL−1.

In embodiment 57 provided herein is a cell containing the composition of any previous embodiment. In embodiment 58 provided herein is the cell of embodiment 56 wherein the cell is a human cell. In embodiment 59 provided herein is the cell of embodiment 58 wherein the cell is an immune cell or a stem cell. In embodiment 60 provided herein is the cell of embodiment 59 wherein the cell is an immune cell. In embodiment 61 provided herein is the cell of embodiment 60 wherein the cell is a T cell. In embodiment 62 provided herein is the cell of embodiment 59 wherein the cell is a stem cell. In embodiment 63 provided herein is the cell of embodiment 62 wherein the cell is an induced pluripotent stem cell (iPSC).

In embodiment 64 provided herein is a method comprising inserting a composition of any one of embodiments 1 through 56 into a cell. In embodiment 65 provided herein is the method of embodiment 64 wherein inserting the composition into the cell comprises electroporation.

In embodiment 66 provided herein is a method for modifying a target polynucleotide comprising (i) contacting the composition of any one of embodiments 40 through 56 and (ii) allowing the nuclease and the guide nucleic acid to modify a targeted genomic region. In embodiment 67 provided herein is the method of embodiment 66 wherein the composition is a composition of any one of embodiments 51 through 56. In embodiment 68 provided herein is the method of embodiment 66 or embodiment 67 wherein the target polynucleotide is a genome or a portion of a genome within a cell. In embodiment 69 provided herein is the method of embodiment 68 wherein the cell is a human cell. In embodiment 70 provided herein is the method of embodiment 69 wherein the cell is an immune cell or a stem cell. In embodiment 71 provided herein is the method of embodiment 70 wherein the cell is an immune cell. In embodiment 72 provided herein is the method of embodiment 71 wherein the cell is a T cell. In embodiment 73 provided herein is the method of embodiment 70 wherein the cell is a stem cell. In embodiment 74 provided herein is the method of embodiment 73 wherein the stem cell is an iPSC In embodiment 75 provided herein is the method of any one of embodiments 67 through 74 wherein the donor template comprises a mutation in a PAM within 50 nucleotides of the target nucleotide sequence in the target polynucleotide. In embodiment 76 provided herein is the method of any one of embodiments 68 through 74 wherein the composition is a composition of embodiment 67 and the donor template comprises a polynucleotide coding for a polypeptide to be expressed by the cell. In embodiment 77 provided herein is the method of embodiment 76 wherein the polypeptide to be expressed by the cell comprises a chimeric antigen receptor (CAR) or a portion thereof. In embodiment 78 provided herein is the method of embodiment 77 wherein the cell is a human T cell or a human iPSC. In embodiment 79 provided herein is the method of embodiment 77 wherein the cell is a human T cell. In embodiment 80 provided herein is the method of embodiment 77 wherein the cell is a human iPSC.

In embodiment 81 provided herein is a composition comprising a first polynucleotide coding for a polypeptide comprising a nucleic acid-guided nuclease comprising a CRISPR Type V nuclease polypeptide, wherein the polynucleotide has less than 75% sequence identity to SEQ ID NO: 22. In embodiment 82 provided herein is the composition of embodiment 81 wherein the nuclease polypeptide comprises at least 1, 2, 3, 4, or 5 NLSs, wherein each of the NLSs is at or near the N-terminus or the C-terminus of the nuclease polypeptide. In embodiment 83 provided herein is the composition of embodiment 82 wherein one or more of the NLSs comprises an NLS of the SV40 virus large T-antigen, an NLS from nucleoplasmin, e.g. a nucleoplasmin bipartite NLS, a c-myc NLS; a hRNPA1 M9 NLS; an IBB domain of importin-alpha NLS; a myoma T protein NLS; a sequence from human p53 NLS; a sequence of mouse c-abl IV NLS; a sequence of influenza virus NS1 NLS; a sequence of Hepatitis virus delta antigen NLS; a sequence of mouse Mx1 protein NLS; a sequence of human poly(ADP-ribose) polymerase NLS; a sequence of steroid hormone receptors (human) glucocorticoid NLS; and/or a sequence of EGL-13 NLS. In embodiment 84 provided herein is the composition of embodiment 83 wherein one or more of the NLSs comprises an NLS of the SV40 virus large T-antigen. In embodiment 85 provided herein is the composition of embodiment 84 wherein the NLS or NLSs comprises the sequence of SEQ ID NO: 5. In embodiment 86 provided herein is the composition of any one of embodiments 83 through 85 wherein one or more of the NLSs comprises an NLS from nucleoplasmin. In embodiment 87 provided herein is the composition of embodiment 86 wherein the nucleoplasmin NLS comprises the sequence of SEQ ID NO: 6. In embodiment 88 provided herein is the composition of any one of embodiments 83 through 87 wherein one or more of the NLSs comprises a c-myc NLS. In embodiment 89 provided herein is the composition of embodiment 88 wherein the c-myc NLS comprises the sequence of SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 21. In embodiment 90 provided herein is the composition of embodiment 88 wherein the c-myc NLS comprises the sequence SEQ ID NO: 21. In embodiment 91 provided herein is the composition of any one of embodiments 83 through 90 wherein one or more of the NLSs comprises a sequence of EGL-13 NLS. In embodiment 92 provided herein is the composition of embodiment 91 wherein the EGL-13 NLS comprises the sequence of SEQ ID NO: 107. In embodiment 93 provided herein is the composition of any one of embodiments 82 through 92 wherein the NLS or NLSs is at or near the N-terminus of the polypeptide. In embodiment 94 provided herein is the composition of any one of embodiments 81 through 93 wherein the first polynucleotide comprises a polynucleotide coding for a purification tag. In embodiment 95 provided herein is the composition of embodiment 94 wherein the purification tag is at or near the N-terminus of the nuclease polypeptide. In embodiment 96 provided herein is the composition of embodiment 94 or 95 wherein the purification tag comprises a poly-his tag, such as a Gly-6×His tag (SEQ ID NO: 421) or Gly-8×His tag (SEQ ID NO: 422); short epitope tags, e.g., FLAG, hemagglutinin (HA), c-myc, T7, Glu-Glu; maltose binding protein (mbp); N-terminal glutathione S-transferase (GST); or calmodulin binding peptide (CBP). In embodiment 97 provided herein is the composition of embodiment 96 wherein the purification tag comprises a poly-his tag. In embodiment 98 provided herein is the composition of embodiment 97 wherein the purification tag comprises a gly-6×His tag (SEQ ID NO: 421). In embodiment 99 provided herein is the composition of embodiment 97 wherein the purification tag comprises a gly-8×His tag (SEQ ID NO: 422). In embodiment 100 provided herein is the composition of any one of embodiments 81 through 99 wherein the Type V CRISPR nuclease polypeptide comprises a cleavage site. In embodiment 101 provided herein is the composition of embodiment 100 wherein the cleavage site is at or near the N-terminus of the nuclease polypeptide. In embodiment 102 provided herein is the composition of embodiment 100 or 101 wherein the cleavage site comprises a Tobacco Etch Virus (TEV) cleavage site. In embodiment 103 provided herein is the composition of embodiment 102 wherein the cleavage site comprises the sequence of SEQ ID NO: 108. In embodiment 104 provided herein is the composition of embodiment 103 comprising 5 NLSs at or near the N-terminus of the polypeptide, a purification tag, and the cleavage site, wherein the cleavage site is after the purification tag. In embodiment 105 provided herein is the composition of any one of embodiments 81 through 104 wherein the polynucleotide codes for a polypeptide comprising a sequence at least 60, 70, 80, 85, 90, 95, 98, 99%, or 100%, identical, preferably at least 80%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% identical to any one of SEQ ID NOs: 109-112 In embodiment 106 provided herein is the composition of any one of embodiments 81 through 105 wherein the polynucleotide codes for a polypeptide comprising a sequence at least 60, 70, 80, 85, 90, 95, 98, 99%, or 100%, preferably at least 80%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% identical identical to SEQ ID NO: 112. In embodiment 107 provided herein is the composition of any one of embodiments 81 through 105 wherein the first polynucleotide comprises a sequence at least 50, 60, 70, 80, 90, 95, 97, or 99% identical, or 100% identical, preferably at least 80%, more preferably at least 90%, even more preferably at least 95%, still more preferably at least 98% identical to SEQ ID NO: 113. In embodiment 108 provided herein is the composition of any one of embodiments 81 through 107 further comprising a second polynucleotide coding for a gNA or portion thereof, wherein the gNA, e.g., gRNA, comprises a spacer sequence that targets a target nucleotide sequence within a polynucleotide, or a polynucleotide coding for the gNA, e.g., gRNA, wherein the gNA, e.g., gRNA is compatible with the Type V CRISPR nuclease. In embodiment 109 provided herein is the composition of embodiment 108 wherein the first and second polynucleotides are the same. In embodiment 110 provided herein is the composition of any one of embodiments 81 through 109 further comprising third polynucleotide that comprises a donor template.

In embodiment 111 provided herein is a vector comprising the polynucleotide or polynucleotides of any one of embodiments 81 through 110.

In embodiment 112 provided herein is a cell comprising a composition of any one of embodiments 81 through 110. In embodiment 113 provided herein is the composition of embodiment 112 wherein the cell is a human cell. In embodiment 114 provided herein is the composition of embodiment 113 wherein the cell is an immune cell or a stem cell. In embodiment 115 provided herein is the composition of embodiment 113 wherein the cell is an immune cell. In embodiment 116 provided herein is the composition of embodiment 115 wherein the cell is T cell. In embodiment 117 provided herein is the composition of embodiment 113 wherein the cell is a stem cell. In embodiment 118 provided herein is the composition of embodiment 117 wherein the cell is an iPSC.

In embodiment 119 provided herein is a method comprising inserting the composition of any one of embodiments 81 through 111 into a cell. In embodiment 120 provided herein is the method of embodiment 119 wherein inserting the composition into the cell comprises electroporation.

In embodiment 121 provided herein is a method comprising (i) inserting a composition of any one of embodiments 81 through 107 into a cell and (ii) inserting a gNA, e.g. a gRNA, compatible with the Type V CRISPR nuclease coded for by the composition, into the cell. In embodiment 122 provided herein is the method of embodiment 121 wherein steps (i) and (ii) comprise electroporation.

While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby. 

1.-122. (canceled)
 123. A composition comprising a nucleic acid-guided nuclease comprising a Type V CRISPR nuclease polypeptide comprising at least three nuclear localization signals (NLS) at or near the N-terminus or the C-terminus of the polypeptide, wherein at least two of the NLSs are at or near the N-terminus of the polypeptide, or a polynucleotide encoding the nuclease.
 124. The composition of claim 123 wherein the nuclease is a Type Va nuclease.
 125. The composition of claim 123 wherein the Type V CRISPR nuclease polypeptide has at least 80% sequence identity with SEQ ID NO:
 1. 126. The composition of claim 123 wherein the Type V CRISPR nuclease polypeptide comprises four NLSs, each of which is at or near the N-terminus or the C-terminus of the polypeptide.
 127. The composition of claim 123 wherein the Type V CRISPR nuclease polypeptide comprises at least five NLSs, each of which is at or near the N-terminus or the C-terminus of the polypeptide.
 128. The composition of claim 123 wherein at least three of the NLSs are at or near the N-terminus of the polypeptide.
 129. The composition of claim 126 wherein at least four of the NLSs are at or near the N-terminus of the polypeptide.
 130. The composition of claim 127 wherein the 5 NLSs are at or near the N-terminus of the polypeptide.
 131. The composition of claim 130 wherein the polypeptide comprises a sequence at least 80%, identical to any one of SEQ ID NOs: 109-112.
 132. The composition of claim 123 wherein at least two of the NLSs have different nuclear localization mechanisms.
 133. The composition of claim 123 wherein one or more of the NLSs comprises an NLS of the SV40 virus large T-antigen, an NLS from nucleoplasmin, e.g. a nucleoplasmin bipartite NLS, a c-myc NLS; a hRNPA1 M9 NLS; an IBB domain of importin-alpha NLS; a myoma T protein NLS; a sequence from human p53 NLS; a sequence of mouse c-abl IV NLS; a sequence of influenza virus NS1 NLS; a sequence of Hepatitis virus delta antigen NLS; a sequence of mouse Mx1 protein NLS; a sequence of human poly(ADP-ribose) polymerase NLS; a sequence of steroid hormone receptors (human) glucocorticoid NLS; and/or a sequence of EGL-13 NLS.
 134. The composition of claim 123 wherein the Type V CRISPR nuclease polypeptide further comprises a purification tag at or near the N-terminus of the nuclease polypeptide.
 135. The composition claim 134 wherein the Type V CRISPR nuclease polypeptide comprises a cleavage site at or near the N-terminus of the nuclease polypeptide.
 136. The composition of claim 135 comprising 5 NLSs at or near the N-terminus of the polypeptide, a purification tag, and the cleavage site, wherein the cleavage site is after the purification tag.
 137. The composition of claim 136 comprising a sequence at least 80%, identical to SEQ ID NO: 111 or
 112. 138. The composition of claim 123 further comprising a guide nucleic acid (gNA), comprising a spacer sequence that targets a target nucleotide sequence within a polynucleotide, or a polynucleotide coding for the gNA, wherein the gNA, is compatible with the Type V CRISPR nuclease.
 139. The composition of claim 138 wherein the gRNA is a dual gRNA.
 140. A method for modifying a target polynucleotide comprising: (A) contacting the polynucleotide with a composition comprising (i) a nucleic acid-guided nuclease comprising a Type V CRISPR nuclease polypeptide comprising at least three nuclear localization signals (NLS) at or near the N-terminus or the C-terminus of the polypeptide, wherein at least two of the NLSs are at or near the N-terminus of the polypeptide, or a polynucleotide encoding the nuclease, and (ii) a guide RNA compatible with the nuclease and comprising a spacer sequence complementary to the target polynucleotide or a portion thereof; and (B) allowing the nuclease to modify the target polynucleotide.
 141. The method of claim 140 wherein the target polynucleotide is a genome or a portion of a genome within a cell.
 142. The method of claim 140 wherein the guide RNA is a dual guide RNA.
 143. The method of claim 140 wherein the nuclease is a Type Va nuclease.
 144. The method of claim 140 wherein the Type V CRISPR nuclease polypeptide has at least 80% sequence identity with SEQ ID NO:
 1. 145. The method of claim 140 wherein the Type V CRISPR nuclease polypeptide comprises four NLSs, each of which is at or near the N-terminus or the C-terminus of the polypeptide.
 146. The method of claim 140 wherein the Type V CRISPR nuclease polypeptide comprises at least five NLSs, each of which is at or near the N-terminus or the C-terminus of the polypeptide.
 147. The method of claim 146 wherein at least three of the NLSs are at or near the N-terminus of the polypeptide.
 148. The method of claim 146 wherein at least four of the NLSs are at or near the N-terminus of the polypeptide.
 149. The method of claim 146 wherein the 5 NLSs are at or near the N-terminus of the polypeptide. 